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Billionaire Richard Branson has invested in everything from commercial space travel to record labels. Now he is getting into the human genome business.

His blank-check special-purpose company, VG Acquisition Corp. (ticker: VGAC), is merging with the gene-testing company 23andMe and will list it publicly on the New York Stock Exchange under the ticker ME. Under the deal, which values the company at around $3.5 billion, existing shareholders of the gene-testing firm will own 81% of the business.

Branson and Anne Wojcicki, the CEO of 23andMe, will each invest $25 million in a $250 million private investment in public equity, or PIPE. Other investors include funds managed by Fidelity, Altimeter Capital, Casdin Capital, and Foresite Capital. It is expected to close in the second quarter.

The transaction will bring 23andMe gross proceeds of up to $759 million, according to a statement disclosing the deal. That includes the $250 million PIPE and up to $509 million in a VG Acquistion trust account.

For Branson, it is a foray into the booming health-care services industry. 23andMe sells an at-home testing kit that has become popular with consumers who want to learn about their genetic backgrounds. The information can reveal details about genetic health risks in addition to ancestry.

Test users also have the option to participate in genetic research, which 80% accept. The insights from this research can be used to develop future therapies for cancer, heart, and lung disease, among others, the company said.

We have a huge opportunity to help personalize the entire experience at scale, allowing individuals to be more proactive about their health and wellness, said Wojcicki. Through a genetics-based approach, we fundamentally believe we can transform the continuum of healthcare.

Branson said in the same statement that he was excited to see 23andMe make a positive difference to more people.

Consumer genetic testing fits into the growing segment of personalized medicine and health care. Its also an area of controversy over privacy issues.

In 2018, 23andMe joined forces with GlaxoSmithKline (GSK) in a four-year project to use the genetic data 23andMe gathers to develop new drugs.

VG Acquisition shares jumped more than 14% on Thursday, compared with a 0.9% gain in the S&P 500.

Write to Liz Moyer at Liz.Moyer@barrons.com

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Richard Bransons SPAC to Merge With Gene-Testing Firm 23andMe - Barron's

Patients with head and neck squamous cell carcinoma (HNSCC), the sixth most common epithelial cancer worldwide, are treated with surgery, chemotherapy and radiotherapy. In addition, targeted agents, including an EGFR monoclonal antibody (mAb) inhibitor and two programmed cell death protein 1 (PD-1) inhibitors, have been approved by the U.S. Food and Drug Administration for HNSCC treatment, but response rates are moderate.

In this study, researchers led by Baylor College of Medicine, Johns Hopkins University and the National Cancer Institutes Clinical Proteomic Tumor Analysis Consortium (CPTAC) investigated what new insight proteogenomic analysis might offer into understanding why certain patients respond to certain treatments while other patients do not. They propose that their findings may help better match patients to an appropriate course of treatment in the future.

The team profiled proteins, phosphosites (a site on a protein associated with phosphorylation) and signaling pathways in 108 human papillomavirus-negative HNSCC tumors in order to understand how genetic aberrations drive tumor behavior and response to therapies.

We found three subtypes of head and neck squamous cell carcinoma, and each subtype may be a good candidate for a different type of therapy EGFR inhibitors, CDK inhibitors or immunotherapy, saidDr. Bing Zhang, lead contact of the study and professor in theLester and Sue Smith Breast Centerand theDepartment of Molecular and Human Geneticsat Baylor. We also identified candidate biomarkers that could be used to match patients to effective therapies or clinical trials.

One important finding involved matching HNSCC patients to EGFR mAb inhibitors. Cetuximab, an EGFR mAb medication, was approved by the FDA in 2006 as the first targeted therapy for HNSCC, however the success rate for this treatment is low. Moreover, EGFR amplification or overexpression cannot predict response to EGFR mAbs. In this study, researchers found that EGFR ligands, instead of EGFR itself, act as the limiting factor for EGFR pathway activation. When ligand is low, the downstream pathway will not be triggered, even if EGFR protein is highly overexpressed.

We proposed that the EGFR ligand should be used as a biomarker, rather than EGFR amplification or overexpression, to help select patients for the EGFR monoclonal antibody treatment, said Zhang, a member of the Dan L Duncan Comprehensive Cancer Center, a Cancer Prevention & Research Institute of Texas (CPRIT) Scholar and aMcNair Scholarat Baylor.

Tumors with high EGFR amplification do not necessarily have high levels of EGFR ligands, which may underlie their lack of response to EGFR mAb therapy. The team confirmed this hypothesis by analyzing previously published data from patient-derived xenograft models and a clinical trial.

Additionally, tracking a key tumor suppressor known as Rb (retinoblastoma), the research team identified a striking finding that suggests that Rb phosphorylation status could potentially be a better indicator of a patients response to CDK4/6 inhibitor therapy. The study showed that the many mutations in the genes regulating CDK4/6 activity were neither necessary nor sufficient for activation of CDK4/6.

The team found that the CDK4 activity was best measured through Rb phosphorylation measurements, thus identifying a potential measure for patient selection in CDK inhibitor clinical trials.

The research team also found important insights into the effectiveness of immunotherapy. PD-1 inhibitors target the interaction between immune checkpoints PD-1 and PD-L1, but success rates of immunotherapy are low, even when PD-L1 expression is used for patient selection. The researchers examined tumors with high expression of PD-L1 and found that when a tumor overexpresses PD-L1, it also upregulates other immune checkpoints, thus allowing the tumor growth despite the use of PD-1 inhibitors.

This observation suggests that PD-1- and PD-L1-activated tumors with hot immune environments may require multiple types of immunotherapy, which target different immune checkpoint proteins, to be effective.Conversely, tumors with cold immune environments are not good targets for immunotherapy.

Immune-cold tumors are tumors that contain few if any infiltrating immune T cells. Examination of how a tumor becomes immune-cold showed that the problem stems from a flaw in its antigen presentation pathway, a first step toward triggering an immune response against tumor antigens. In immune-cold tumors multiple key gene components of the antigen presentation pathway were deleted. As a result, although tumor antigens are being expressed, the immune system is not able to recognize them on the surface of cancer cells and therefore fails to activate the bodys defense system against the tumor. These deletions have the potential to be effective targets for future therapies.

This study extends our biological understanding of HPV-negative HNSCCs and generates therapeutic hypotheses that may serve as the basis for future studies and clinical trials toward molecularly-guided precision medicine treatment of this aggressive cancer type, saidDr. Daniel W. Chan, co-corresponding author of the study, professor of pathology and oncology, and director of theCenter for Biomarker Discovery and Translationat theJohns Hopkins University School of Medicine.

Find all the details of this study and a full list of contributing authors in the journalCancer Cell.

This work was supported by grants U24 CA210954, U24 CA210985, U24 CA210972, U24 CA210979, U24 CA210986, U24 CA214125, U24 CA210967, and U24 CA210993 from the National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC), by a Cancer Prevention Institute of Texas (CPRIT) award RR160027, by grant T32 CA203690 from the Translational Breast Cancer Research Training Program, and by funding from the McNair Medical Institute at the Robert and Janice McNair Foundation.

By Molly Chiu

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Using proteogenomics to improve the treatment of squamous cell carcinoma - Baylor College of Medicine News

SEATTLE, Feb. 3, 2021 /PRNewswire/ --Just like us, immune cells need fuel to do their jobs. Despite the tight links between human health including our immunity and how our bodies process what we eat, the intersection of immunology and metabolism remains a poorly understood area of human biology.

New awards announced today by The Paul G. Allen Frontiers Group, a division of the Allen Institute, aim to improve that understanding by supporting four research projects in the emerging field of immunometabolism. The projects, which are led by 10 new Allen Distinguished Investigators working in teams of two or three lead investigators per award, will explore new avenues of basic biology, health, disease, and technology development, all focused on unanswered questions about how the immune system and metabolism work together.

In recent years, as Frontiers Group staff met with scientific experts to identify future areas of interest, the topic of metabolism and its intersection with the immune system kept coming up, said Frontiers Group Director Kathy Richmond, Ph.D., M.B.A. As they delved into the unknowns, Richmond and her team realized that any significant progress in these areas could improve human health.

"In so many diseases, a tipping point is reached where entire systems in our bodies are thrown off balance. Studying the complex and fascinating interactions between the immune system and energy metabolism will give us a better understanding of what it means to be healthy and how it might be possible to return those systems to balance after damage or disease," Richmond said. "The innovative and pioneering visions of these four teams of Allen Distinguished Investigators span a variety of approaches to tackle this exciting area of biomedical research."

Each award confers $1.5 million in funding over three years for a total of $6 million awarded for immunometabolism research. The Frontiers Group, founded by the late philanthropist Paul G. Allen in 2016, recommends funding from the Paul G. Allen Family Foundation to researchers around the world whose work has the potential to accelerate scientific discoveries or launch entirely new avenues of exploration.The Allen Distinguished Investigator program was launched in 2010 by Allen to back creative, early-stage research projects in biology and medical research that would not otherwise be supported by traditional research funding programs. Including the 10 new investigators announced today, a total of 92 Allen Distinguished Investigators have been appointed.

The four new research projects include research on human disease, basic biology of the mammalian immune system, and technology development that could impact many areas of immunology and metabolism research.

"The whole field of immunometabolism is relatively new, and it's a great time to be studying this area because there are also new technologies that allow for exploration of metabolic processes within cells and tissues," said Dan Littman , M.D., Ph.D., a professor of immunology and microbiology at NYU Langone Health. "It's an exciting and emerging area, and there aren't many other avenues for funding immunometabolism research as of yet."

Meet the new Allen Distinguished Investigators

Will Bailis, Ph.D.Children's Hospital of PhiladelphiaChris Bennett, M.D.University of PennsylvaniaRuaidhr Jackson, Ph.D.Harvard Medical SchoolAll of us are made up of trillions of cells, yet it is unclear how these cells simultaneously behave as individuals and as part of a collective that makes up who we are. Drs. Will Bailis, Chris Bennett and Ruaidhri Jackson are leading a project to better understand the many links between immunity and metabolism at the scale of individual cells, organs and the entire body. These inextricable links how our diet affects our immune system, and how our immune cells in turn change metabolism tie into all aspects of human health and disease, including cancer, diabetes and heart disease. Using laboratory mice, the researchers will study how an animal's food affects energy production inside immune cells by genetically engineering those cells to "ignore" changes in diet. In tandem, they will study how one particular type of immune cell, known as tissue resident macrophages, uses metabolism to govern not only its own cellular function, but the function of tissues and the entire body.

Aida Habtezion, MD, MSc.Stanford University School of MedicineNandita Garud, Ph.D., MS.University of California, Los AngelesCarolina Tropini, Ph.D.University of British ColumbiaInflammatory bowel disease, or IBD, is a class of immune diseases that stem from chronic inflammation in the intestines. Patients with IBD have widely varied symptoms and responses to treatment which can't be fully explained by human genetics. Drs. Aida Habtezion, Nandita Garud and Carolina Tropini are leading a project to explore how patients' immune responses, metabolism, gut microbiomes and environments may contribute to that variability, using a registry of hundreds of IBD patient volunteers. Better understanding the details of variation between patients, and the reasons behind that diversity, could lead to better, more tailored treatments for this class of often crippling illnesses.

Russell Jones, Ph.D.Van Andel InstituteYasmine Belkaid, Ph.D.National Institute for Allergies and Infectious DiseaseLike all cells, our immune cells need energy from the food we eat to do their jobs. Drs. Russell Jones and Yasmine Belkaid have recently found that T cells, an important type of immune cell that surveys the body and detects and eliminates infected cells, use multiple kinds of fuel when they are working their hardest. Now, they are leading a project to better understand T cells' preferred fuel sources, uncovering which types of T-cell metabolism are needed for optimal infection-fighting and which types might lead to immune dysfunction.

Jennifer Prescher, Ph.D.Michelle Digman, Ph.D.University of California, IrvineTo better understand the immune system and how it dovetails with metabolism, researchers need better toolkits to track and manipulate multiple kinds of cells and molecules at once, over time, in a living animal. Drs. Jennifer Prescher and Michelle Digman are leading the development of a new technique to shine "biological flashlights" on many different immune- and metabolism-related molecules at the same time. The technique, which they dub bioluminescent phasor, will ultimately yield a large toolkit of optical tags that can light up multiple processes or proteins in the laboratory mouse's immune system at once. Once complete, the toolkit would be available for any research lab to use, opening new avenues for discoveries about the immune system and its relationship to our diet.

About The Paul G. Allen Frontiers GroupThe Paul G. Allen Frontiers Group, a division of the Allen Institute,is dedicated to exploringthe landscape of bioscience to identify and foster ideas that will change the world. The Frontiers Group recommends funding through award mechanisms to accelerate our understanding of biology, including: Allen Discovery Centers at partner institutions forleadership-driven, compass-guided research; and Allen Distinguished Investigatorsforfrontier explorations with exceptional creativity and potential impact.The Paul G. Allen Frontiers Groupwas foundedin 2016 by the late philanthropist and visionary Paul G. Allen. For more information, visit allenfrontiersgroup.org.

About the Paul G. Allen Family Foundation

For more than four decades the Paul G. Allen Family Foundation has focused on changing the trajectory of some of the world's toughest problems. Founded by philanthropists Jody Allen and the late Paul G. Allen, co-founder of Microsoft, the Foundation initially invested in community needs across the Pacific Northwest with a focus on regional arts, under-served populations, and the environment. Today, the Foundation supports a global portfolio of frontline partners working to preserve ocean health, protect wildlife, combat climate change, and strengthen communities. The Foundation invests in grantees to leverage technology, fill data and science gaps, and drive positive public policy to advance knowledge and enable lasting change.

Media Contact: Rob Piercy, Director, Media Relations206.548.8486 | [emailprotected]

SOURCE The Paul G. Allen Frontiers Group

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New Allen Distinguished investigators will tackle unanswered questions about metabolism and the immune system - PRNewswire

Today on In the Hive, a primer on coronavirus variants. Three variants of SARS-Cov-2 have drawn the attention of health officials because they may spread more easily or in some cases may be more deadly than the original. The Centers for Disease Control and Prevention says that the so-called UK Variant has now been detected in more than half of U.S. states including Utah, while the Brazilian variant has been found in Minnesota and the South African variant in Maryland and South Carolina. How do viruses mutate? And what should we be doing to protect ourselves? Dr. Stephen Goldstein, a post-doctoral researcher with the University of Utahs Department of Human Genetics says that all the same rules apply for trying to curb the spread of these versions of the virus. Goldstein also says the vaccines we have appear to build an immune response to these variants, which means there is, still, a light at the end of the pandemic tunnel.

Guest:Dr. Stephen Goldstein, Post-doctoral researcher at the University of Utahs Dept. of Human Genetics

Podcast: Play in new window | Download (32.2MB)

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Coronavirus variants, vaccines, and where the pandemic is headed - KCPW

CAMBRIDGE, Mass., Feb. 2, 2021 /PRNewswire/ --Eisai Inc., the U.S. pharmaceutical subsidiary of Eisai Co., Ltd. and BioLabs announced today the launch of the Eisai Innovation Center BioLabs, a shared lab and office space for start-ups aiming to innovate in the complex field of neurological diseases. The incubator space is located at the Eisai Center for Genetics Guided Dementia Discovery (G2D2) facility and will become part of BioLabs' national biotechnology network.

"We are excited to announce this collaboration with BioLabs," said Nadeem Sarwar, Ph.D. and President of G2D2. "This specialized incubator will be the first of its kind. With BioLabs' focus on building ecosystems that foster rapid innovation combined with G2D2's state-of-the-art technology to support neurological research, we believe the creation of the Eisai Innovation Center BioLabs will fuel new scientific discoveries and insights. With more than 50 million people globally living with dementia1, there has never been a greater need for the discovery of novel approaches to prevention and treatment."

Housed in the G2D2 facility, the Eisai Innovation Center BioLabs aims to host five to seven neurology-focused start-ups and provide the infrastructure and support to help build their biotech companies. The facility was custom-designed for discovery research, including capabilities for in-vitro biology, molecular and cellular biology including BioSafety Level 2 tissue culture, microscopy, chemical and structural biology and screening. Companies hosted at this incubator will have the opportunity to access the BioLabs network, and interact with the Eisai network, including G2D2 and Eisai's investment arm, Eisai Innovation Inc.

"Launching this incubator space in partnership with BioLabs is an important milestone in our relentless pursuit of a cure for neurological diseases, including Alzheimer's disease, and the fulfillment of our human health care mission. In this new specialized model, we want to advance beyond offering only co-working space," said Vanessa Almendro, MBA, Ph.D. and Head of Strategy and External Innovation at G2D2. "By providing scientific support and enabling potential collaborative opportunities, the Eisai Innovation Center BioLabs is pioneering in providing unique, broad and tailored support to the most prominent biotech companies developing transformative therapies, devices and digital solutions for patients suffering from neurological disorders."

The integration with BioLabs, a national, membership-based network of shared lab and office facilities located in key biotech innovation clusters, empowers companies to rapidly launch their operations in a full-equipped, ready-to-use facility, while collaborating with other innovators in the field.

"The custom-designed space at G2D2 is an ideal home for the Eisai Innovation Center BioLabs. The open-lab layout naturally fosters integration between entrepreneurs, all focused on understanding and advancing the field of neurological diseases. Interacting with a community of peers, specifically within a specialized area of research, sparks collaboration and can significantly fast track a start-up's evolution," said Adam Milne, Chief Operating Officer at BioLabs.

A joint selection committee with members of Eisai Inc., Eisai Innovation Inc. and BioLabs representatives will select the companies to be invited. The selection committee will prioritize start-ups focused on neurology, aligned with Eisai's human health care mission and showing strong potential to develop curative therapeutics. To learn more about the incubator, visit our website.

About Eisai Inc. At Eisai Inc., human health care (hhc)is our goal. We give our first thoughts to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to discover and develop innovative therapies to help address unmet medical needs.

Eisai is a fully integrated pharmaceutical business that operates in two global business groups: oncology and neurology (dementia-related diseases and neurodegenerative diseases). Our U.S. headquarters, commercial and clinical development organizations are located in New Jersey; our discovery labs are in Massachusetts and Pennsylvania; and our global demand chain organization resides in Maryland and North Carolina. To learn more about Eisai Inc., please visit us at http://www.eisai.com/US and follow us on Twitter and LinkedIn.

About Eisai Innovation, Inc.Eisai Innovation, Inc.(EII) is a subsidiary of Eisai Inc. It is a strategic investment organization aspiring to identify synergies between the scientific community and the Eisai network of companies. EII contributes toour human health care (hhc)mission by prioritizing disease prevention, prediction and treatment through global investments and research collaboration.

About G2D2Eisai Center for Genetics Guided DementiaDiscovery (G2D2) is the first research center focused on immunodementia. As part of Eisai's Neurology Business Group, G2D2 draws upon Eisai's cutting-edge strengths in human genetics, data sciences and precision chemistry to accelerate discovery of breakthrough immunodementia precision therapeutics.

G2D2 is located in the Alewife Research Center in the Alewife area, in the north-west part of Cambridge, which is one of the world's leading biotechnology clusters where private research organizations in addition to academic institutions such as Harvard University, the Massachusetts Institute of Technology and Tufts University are concentrated. Leveraging the benefits of the location, a research space that can be used by external organizations will be set up at G2D2 to enhance collaboration with outstanding researchers and open innovation initiatives to promote immunodementia drug discovery.

About BioLabsBioLabsis a membership-based network of shared lab facilities located in the nation's key biotech innovation clusters, designed exclusively for high-potential, early-stage life science companies. It offers co-working environments that pair premium, fully equipped and supported lab and space with unparalleled access to capital and industry partners. Find out more athttps://www.biolabs.io/

References

Contact:

Eisai Inc. Libby Holman201-753-1945 [emailprotected]

SOURCE Eisai Inc.

http://www.eisai.com

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Eisai and BioLabs Partner to Create the Eisai Innovation Center BioLabs - PRNewswire

The COVID-19 pandemic has hit some Americans particularly hard.

Older adults, people with certain preexisting health conditions, and members of ethnic and racial minorities are more likely than others to develop serious symptoms of the disease. Theyve faced higher rates of hospitalization and higher rates of death from COVID-19.

To help community members learn how certain risk factors affect the chances of hospitalization in people whove developed COVID-19, the consumer genomics company 23andMe has launched a new interactive tool called the COVID-19 Severity Calculator.

Its interesting because it turns every citizen who looks at it into a bit of an investigator, said Dr. Robert C. Green, MPH, a medical geneticist and physician-scientist at Brigham and Womens Hospital in Boston, Massachusetts.

You can change the age, you can change the body mass index, you can change the ethnicity and see how it influences the risk of hospitalization, he continued.

The tool offers insights into some of the risk factors for hospitalization from COVID-19, but the company notes that its not intended to predict an individual users risk and doesnt take into account genetic risk factors. The tool does not take into account all of the possible risk factors that can affect how the disease develops.

We created the Severity Calculator because people who have visited 23andMes COVID-19 Information Center have consistently been asking for more information about the severity of the virus infection and what factors into why it impacts some people harder than others, Janie F. Shelton, PhD, MPH, a senior scientist at 23andMe, said in a company press release

The COVID-19 Severity Calculator only incorporates nongenetic risk factors for hospitalization from COVID-19.

They make it clear that this is not based on your genetics. But you have to read that. Its not like its in huge bold letters, Green told Healthline.

The tools algorithm is based on data related to age, sex, ancestry, weight, height, exercise frequency, and certain health conditions. Those conditions include fatty liver disease, high blood pressure, and type 2 diabetes.

Green speculates that the company might eventually incorporate genetic data into the tool as more insights on genetic risk factors become available.

I dont know, but I suspect they will be trying to integrate genetic data into it as the weeks go by and they get more [data], he said.

To develop the COVID-19 Severity Calculator, 23andMe drew on findings from its own COVID-19 Research Study.

The company launched this project in April 2020 to identify and study genetic and non-genetic factors that may affect how COVID-19 develops among members of its customer base.

Study participants share saliva samples and complete online questionnaires about their health, including their experiences with COVID-19.

Nearly 10,000 participants report they have tested positive for the virus. Roughly 750 report being hospitalized with severe symptoms of the disease.

The participants in this study do not represent the general population of the United States, reports 23andMe.

The company also notes that neither the study nor the risk calculator incorporate findings from people who have died from COVID-19.

COVID-19 can cause a wide range of symptoms, ranging from mild to life threatening. Multiple research groups around the world are studying how genetic factors may affect those symptoms and how COVID-19 develops.

I am confident that genetics has a role in disease onset and severity, Michael P. Snyder, PhD, chair of the department of genetics and director of the Center for Genomics and Personalized Medicine at Stanford University in California, told Healthline.

Right now, blood type, which is controlled by genetics, has been associated with COVID-19 in several studies. Other genetic loci are [also beginning to be discovered, he said.

Many scientists who are studying these topics have come together to participate in The COVID-19 Host Genetics Initiative. This international research consortium includes Greens research team, as well as 23andMe.

As researchers learn more about the role of genetics in COVID-19, their findings may help them predict who is at greatest risk of developing severe symptoms. This may help experts learn which groups of people are most likely to benefit from certain treatments, said Snyder.

Genetic insights may also help scientists identify new treatment targets and treatment approaches for COVID-19.

Certain markers may offer clues to specific biological vulnerabilities and specific systems in the body that put you at risk, Green said.

If you can pin down more precisely exactly which genes and variants are more responsible, which proteins those genes produce, youve got a head start on thinking about treatments that can moderate those responses, he added.

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What Experts Think of 23andMe's COVID-19 Risk Calculator - Healthline

Wiesia Woodyatt, Research and Innovation Manager for Stockport NHS Foundation Trust

Stockport NHS Foundation Trust has played a key role in two recent medical research projects which have recently published important findings in the ongoing fight against coronavirus.

The trusts research and innovation team based at Stepping Hill Hospital, together with other staff and patients in both the hospital and community, have contributed toward both the GenOMICC study into the relationship between human genes and Covid-19, and the SIREN study aiming at greater understanding of how far individuals who have recovered from Covid-19 are protected from future infections.

Patients seriously ill with coronavirus in the hospitals ICU took part in the GenOMICC study ('Genetics Of Mortality In Critical Care'), a national research project led by a partnership between the University of Edinburgh and Genomics England.

The study tested how patients genetic makeup could influence how they react to the virus, which will help support the vital search for new treatments.

The GenOMICC study has now successfully identified five genes within DNA that were markedly different between ICU patients and volunteers who did not have Covid-19.

This discovery will help to identify those most at risk, and may assist in fast-tracking new therapies into clinical trials to improve recoveries and help patients survive.

The SIREN study, led by Public Health England, aimed to study and understand whether prior infection with SARS-CoV2 (the virus that causes Covid-19) protects against future infection with the same virus.

Over 100 staff members from Stockport NHS Foundation Trust came forward to assist with this.

The newly published SIREN study found those infected are likely to be protected against reinfection for several months, but could still carry the virus in their nose and throat and transmit it to others.

The study shows a person being infected accounts for an 83 per cent rate of protection against being re-infected themselves, but not against passing on to others.

These continuing studies confirm Stockport NHS Foundation Trusts key role in research on fighting coronavirus, as well as a centre for vaccination against the virus.

Wiesia Woodyatt, Research and Innovation Manager for Stockport NHS Foundation Trust said: "The importance of research remains central to the fight against coronavirus.

"We are proud of the role both our patients and staff have contributed to these studies which have taken important steps forward in these areas."

Stepping Hill Hospital is located in Stockport, Greater Manchester.

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Stockport NHS Trust is at the forefront of Covid-19 research - In Your Area

ATLANTA, Feb. 4, 2021 /PRNewswire/ -- This World Cancer Day, the CDC Foundation announced a multi-year initiative to improve cancer outcomes with anew health empowerment program. Led by the Centers for Disease Control and Prevention (CDC) and the CDC Foundation, EmPOWERed Health is focused on empowering and equipping individuals to become their own health champions. The program will also provide tools and resources that will spark better physician-patient communication and improve shared decision-making.

"Research reveals that people who take an active role in their health have a greater feeling of control, are more likely to adopt positive health behaviors and experience better health outcomes," said Lisa Richardson, MD, MPH, and director of CDC's Division of Cancer Prevention and Control. "This is especially important when trying to prevent or manage a serious condition like cancer. Empowerment can result in more people getting cancer screenings, a greater feeling of control during cancer diagnosis and treatment, and a better care plan for cancer survivors."

Health empowerment has never been more important. The COVID-19 pandemic has been particularly tough for individuals going through cancer, with delayed appointments resulting in heightened anxiety. Cancer screening rates have also declined significantlyscreening appointments for breast, cervical, and colon cancers in March 2020 decreased between 86 percent and 94 percent compared with average volumes in the prior three years, according to a study by the medical record company Epic.

"It's critically important we empower individuals to return to care, especially people of color and lower income populations who are disproportionately affected by cancer," said Judy Monroe, MD, president and CEO of the CDC Foundation. "EmPOWERed Health is a unique initiative that will catalyze individuals to become their own health champions."

This program, with financial support from Amgen, will seek input and involvement from individuals from all backgrounds: members of the general public and oncology community, including people with cancer, their care partners, cancer survivors and healthcare providers. Others involved in this effort will include unexpected partners, like technology, entertainment and social media influencers. Kicking EmPOWERed Health off in March, the CDC Foundation will host a virtual hackathon that leverages open innovation to create bold approaches that can educate, raise awareness and trigger positive action.

"At Amgen, we are committed to improving cancer outcomes for allpatients, including those impacted by healthcare inequity. There is good evidence that empowerment and shared-decision making can have a significant impact," said Darryl Sleep, MD chief medical officer at Amgen, "EmPOWERed Health is an opportunity to build and launch innovation that can improve cancer care, and we are excited to grow our long-standing relationship with CDC and the CDC Foundation with this new initiative."

Both healthcare providers and individuals have a role to play in empowerment, and the program will develop tools for both groups. "As both an oncologist and a cancer survivor, I have been a part of both sides of the cancer experience," said Liz O' Riordan, oncologist and breast cancer survivor."Speaking as a clinician, I cannot emphasize enough the importance of treating your patient as an equal partner in healthcare decision making. As a patient, having the information and confidence to express your opinion makes you feel more in control and able to cope with a challenging situation."

For more information and to receive program updates on EmPOWERed Health, visit: http://www.EmpoweredHealth.organd follow us on Instagram.

About the CDC FoundationThe CDC Foundation helps the Centers for Disease Control and Prevention (CDC) save and improve lives by unleashing the power of collaboration between CDC, philanthropies, corporations, organizations and individuals to protect the health, safety and security of America and the world. The CDC Foundation is the go-to nonprofit authorized by Congress to mobilize philanthropic partners and private-sector resources to support CDC's critical health protection mission. Since 1995, the CDC Foundation has raised over$1 billionand launched more than 1,000 programs impacting a variety of health threats from chronic disease conditions including cardiovascular disease and cancer, to infectious diseases like rotavirus and HIV, to emergency responses, including COVID-19 and Ebola. The CDC Foundation managed hundreds of CDC-led programs inthe United Statesandin more than 140 countries last year. For more information, visithttps://www.cdcfoundation.org. Follow the Foundation onTwitter,Facebook,LinkedIn,InstagramandTikTok.

About the Centers for Disease Control and PreventionThe Centers for Disease Control and Prevention (CDC) works 24/7to protect America from health and safety threats. Whether these threats are global or domestic, chronic or acute, curable or preventable, natural disaster or deliberate attack, CDC is the nation's health protection agency.

AboutAmgenAmgenis committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. Amgenfocuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980,Amgenhas grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential. For more information, visitwww.amgen.comand follow us onwww.twitter.com/amgen.

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http://www.cdcfoundation.org

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CDC Foundation Aims to Improve Cancer Outcomes Through New Initiative Aimed at Education and Empowerment - PRNewswire

The study of a disease is inherently challenging when patients are few and far between, but doctors at the Perelman School of Medicine have reported a new patient-powered approach that may help to revolutionize the study of rare diseases.

The Penn Medicine researchers, in a paper in Cell Reports Medicine, described a new type of patient registry they recently developed for Castleman disease, a rare disorder involving flu-like symptoms, enlarged lymph nodes, and sometimes life-threatening vital organ dysfunction.

The registry, called ACCELERATE, includes an approach in which Castleman disease patients can enroll directly. The researchers found that this patient-powered approach greatly boosted enrollment and the overall availability of data, compared to the traditional approach in which doctors at a few designated sites can enroll their patients. Another innovative component is that the study team requests and extracts data from the full medical record for each patient who enrolls rather than relying on physicians or patients to enter data, significantly increasing the quantity of data included.

One of the greatest barriers to progress for rare diseases is the lack of high-quality, centralized data, says study senior author David Fajgenbaum, an assistant professor of translational medicine and human genetics at the Perelman School of Medicine who directs the Center for Cytokine Storm Treatment & Laboratory and is a patient with Castleman disease. Using this novel, patient-powered study design to centralize high-quality data through ACCELERATE has been transformative for Castleman disease tracking and clinical trial enrollment and may serve as a model for research on thousands of other rare diseases that have no approved therapies.

Read more at Penn Medicine News.

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A patient-powered registry boosts the study of a rare disease | Penn Today - Penn Today

Advances in DNA sequencing have uncovered three classes of mutations within the gene SATB1, which result in three variations of a neurodevelopmental disorder with varying symptoms ranging from epilepsy to muscle tone abnormalities.

The study, co-authored by academics from Oxford Brookes University, University of Lausanne, Radboud University, University of Oxford, University of Manchester, and led by Max Planck Institute for Psycholinguistics (The Netherlands), identified 42 patients with mutations in the gene SATB1 who were all displaying a range of similar symptoms, with varying severity.

The newly identified SATB1-syndrome is characterised by neurodevelopmental delay, intellectual disability, muscle tone abnormalities, epilepsy, behavioural problems, facial dysmorphism, and dental abnormalities.

Dr Dianne Newbury, Senior Lecturer in Medical Genetics and Genomics at Oxford Brookes University said: Previously, just one or two cases of patients with SATB1 variations had been described but it was not recognised as a specific syndrome. Patients displaying these characteristics and their families, will have known that they had an undefined neurological condition, but they wouldnt have known any specific detail about the condition, or why they had it.

We hope that the recognition of this new disorder, and the information about the molecular pathways contributing to it, will help the families and individuals affected understand more about the condition and achieve a diagnosis they would not have had previously.

The mutations were found to belong to three different classes with the first mutation class causing a loss of function of the SATB1 gene and halving the production of the encoded protein, leading to a less severe syndrome characterised by diminished cognitive function, visual problems, and facial dysmorphism.

The second class of mutations encode shorter proteins that are less efficient, ad shows as an intermediary syndrome, characterised as more severe than the first, but less severe than the third.

The third class modify the encoded protein, making it more active. This altered protein is sticky and binds better to DNA, diminishing the expression of genes it regulates and causing a more severe type of disorder, characterised by severe intellectual disability, epilepsy, a motor speech disorder (dysarthria) and specific facial features.

Dr Alexandre Reymond, Director of the Center for Integrative Genomics at the University of Lausanne in Switzerland said: These results demonstrate that each mutation is different and that is essential to understand their mode of action in order to explain the origin of genetic diseases. We must go beyond sequencing, which is only a first step.

The paper, Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction, has been published in The American Journal of Human Genetics.

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Researchers identify rare genetic syndrome caused by gene mutations - Health Europa

Please join us for the latest instalment of the Wright-Fleming Institute,Infection and Immunity Seminar Series

Vanessa Sancho-Shimizus research is focused on identifying inborn errors of immunity underlying life-threatening infections of childhood ranging from invasive bacterial diseases to severe viral infections including herpes simplex encephalitis (HSE), severe COVID-19 disease, and invasive meningococcal disease (IMD).

She obtained her PhD at McGill University in Montreal, Canada on the genetics of host resistance to Salmonella infection. She moved to the laboratory of Human Genetics of Infectious Disease at Necker Enfants Malades Hospital/University Paris Descartes for her postdoc developing an expertise in investigating Mendelian predisposition to childhood HSE, and TLR3-antiviral IFN pathways.

She came to Imperial College in 2012 as a Marie Curie Research Fellow continuing her work on understanding childhood HSE but has also extended the search for Mendelian defects to other infectious phenotypes including severe childhood viral infections and IMD. She has particular interests in the type I IFN signalling pathway and autophagy. She started her own group in 2014, and is a UKRI Future Leaders Fellow and Lecturer in the Department of Infectious Diseases at Imperial College London St Marys Campus.

A recording will be available for college users. Event recording will be available via Teams/WFI seminar series listing page by the following day.https://www.imperial.ac.uk/infectious-disease/research/virology/wright-fleming-seminars/

Click here to join the meetingJoin on your computer or mobile app

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Human Genetics of Life-Threatening Infections | Events - Imperial College London

It's an ancient disease that may have evolved to confer protection against the plague -- but until 20 years ago, it had scientists and doctors flummoxed.

They couldn't explain why those afflicted, often in the same family, had recurring fevers, abdominal pain, troublesome rashes and muscle aches. Known as familial Mediterranean fever, the disease often went undiagnosed for years, and it was sometimes fatal.

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A similar, but unrelated, mystery fever was initially thought to affect families with Scottish and Irish heritage.

"The pain I felt back then, it moved around. One week the pain was in my leg, and the next week my arm would hurt instead," said Victoria Marklund, 47, a Swedish woman who suffered from TRAPS, or tumor necrosis factor receptor-associated periodic syndrome, a disease first identified in a family of Irish and Scottish descent living in the UK city of Nottingham in 1982.

Her father and grandfather died prematurely from kidney complications, which were likely a consequence of the undiagnosed disorder.

Marklund has now received an effective treatment and lives symptom-free -- largely thanks to the work of one US physician and health researcher, Dr. Dan Kastner, a distinguished investigator at the National Institutes of Health who serves as scientific director of the National Human Genome Research Institute.

The Royal Swedish Academy of Sciences on Monday awarded Kastner the prestigious Crafoord Prize, considered a complement -- and for some winners, a precursor to -- a Nobel prize.

"What Dr. Kastner has accomplished is absolutely groundbreaking. The concept of autoinflammatory disorders didn't exist before he identified the cause behind a number of them," said Olle Kmpe, a professor of clinical endocrinology at Karolinska Institutet in Stockholm who is a member of The Royal Swedish Academy of Sciences and chair of the Prize Committee. The academy also selects Nobel laureates.

"His discoveries have taught us a great deal about the immune system and its functions, contributing to effective treatments that reduce the symptoms of disease from which patients previously suffered enormously," Kmpe added.

Breakthrough

Kastner first came across familial Mediterranean fever in a patient with recurring arthritis and high fevers he treated as a rheumatology fellow just months into his first job at the NIH in Bethesda, Maryland, in 1985. That chance diagnosis set him on a 12-year journey to find the gene -- or genes -- responsible for the disease.

"It was known that familial Mediterranean fever was a genetic disease. It was known that it was recessively inherited, but no one knew what the gene was, or even the chromosome," he said.

He traveled to Israel, where he took blood samples from 50 families with familial Mediterranean fever.

It took Kastner seven years to locate the mutation to chromosome 16. It took another five years -- in 1997 -- for Kastner and his team to find the mutated gene itself -- one misprint in a genetic code comprised of 3 billion letters.

After this breakthrough, he stayed at NIH, where he studied undiagnosed patients with similar symptoms. He identified 16 autoinflammatory genetic disorders and found effective treatments for at least 12 of them, establishing a whole new field of medicine.

Now that the full human genome has been mapped, the process of detecting the genetic root of such disorders is quicker, and greater numbers of patients with these rare, unexplained diseases are being helped as a result of Kastner's work.

All-nighters

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There are few images in science more iconic than the DNA double helix structure, discovered in 1953 by James Watson and Francis Crick, two years after Kastner was born. As a seventh grader, he once created a version of the twisted ladder shape using jelly beans and pipe cleaners for a science fair.

Fast-forward to Kastner's medical career, which started in the early heyday of genetic research. He was inspired by the international race in the late '80s to identify the cystic fibrosis gene -- an achievement that at the time was called "one of the most important in human genetics."

His work to identify the gene that caused familial Mediterranean fever had its own element of competition. In the summer of 1997, to beat a rival team led by French researchers, Kastner took a last-minute flight from Bethesda, Maryland, where the NIH is based, to Boston to submit his manuscript detailing the gene mutation that caused familial Mediterranean fever by hand to the journal Cell on a Friday afternoon.

These were the days before papers could be submitted with the click of a mouse. He hoped to publish his work first. Ultimately, the two teams published their papers simultaneously in different journals -- both fortunately arriving at the same finding.

"I love that type of thing," he said. "We still have races to the finish, and there's nothing like a good week of all-nighters."

Kastner had discovered that the gene involved in familial Mediterranean fever produces a protein called pyrin. Normally this helps to activate our innate immune system -- our first line of defense to fight bacteria and viruses.

In this case, however, pyrin made the innate immune system become overactive, resulting in fever, pain and joint inflammation. He went on to study patients with similar and more devastating symptoms -- identifying TRAPS and many more rare diseases.

The family of diseases identified by Kastner are distinct from autoimmune diseases like rheumatoid arthritis and lupus, in which a different branch of the immune system malfunctions.

Transforming lives

What has motivated Kastner for five decades is how his work decoding the genetics of inflammation can inform new treatments and ultimately transform patients' lives.

"There's nothing more gratifying in life and nothing more satisfying scientifically," he said. He plans to step down from his role as scientific director at the NIH in the next few months and then focus his efforts on his clinic, where he has over 3,000 patients enrolled and "find yet more disease genes, understand how they work, and develop new treatments."

"Of course, one can never know how long that will last, but I love doing it, and will continue as long as I can."

In more recent work beginning in 2014, Kastner identified and pioneered treatment for a severely debilitating genetic disorder known as DADA2, short for deficiency of the enzyme ADA2 (adenosine deaminase 2), which can cause recurring fevers and strokes starting in childhood. His research has radically improved the life of the daughter of Dr. Chip Chambers.

"My daughter, who is 23, was sick from age 2. She got very sick late in her teen years. No one could figure it out. We didn't know what was wrong with her," said Chambers, an assistant clinical professor of surgery at Vanderbilt University Medical Center in Nashville, Tennessee, and founder of the DADA2 Foundation.

"She's now at college and the improvement in her quality of life has been dramatic."

Similarly, TRAPS survivor Marklund suffered for years before her diagnosis at the age of 38. Her nephews, who both have TRAPS but have been given medicine from an early age, don't feel the effects of the disease at all, she told The Royal Swedish Academy Of Sciences.

"I doubted many times that anyone would ever figure out what I was suffering from. So now it feels fantastic, to be told what it was, to understand the cause of the disease and that there is medicine that helps."

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Mysterious untreatable fevers once devastated whole families. This doctor discovered what caused them - Gwinnettdailypost.com

In 1953, James Watson and Francis Crick announced that the shape of DNA was a double helix. This monumental discovery of the structure of DNA empowered generations of scientists to unlock many mysteries of the human body.

In the nearly 70 years since that Nobel Prize-winning breakthrough, the Human Genome project sequenced the makeup of the entire human body, and a new at-home genealogy testing industry was born.

Companies including Ancestry.com and 23andMe have capitalized on new technology that allows customers to spit in a tube and mail in their saliva sample to labs to reveal information about their genetic make-up and ancestral origins.

This week on 60 Minutes, top intelligence officials from the United States government told correspondent Jon Wertheim about DNA data aggregation by foreign nations and the potential threat it poses to the United States.

"Sometimes Americans or people around the globe don't even know the value of their DNA, [or] that it even has value," said Bill Evanina, the former Director of the National Counterintelligence and Security Center. "But it's your single, sole identifier of everything about you as a human being."

Evanina served under Presidents Barack Obama and Donald Trump before he resigned from his senate-confirmed position earlier this month. He said each person has a fiduciary responsibility to safeguard their DNA.

When DNA samples are aggregated into large datasets, their value increases.

Law enforcement officials told 60 Minutes they are concerned about the lack of public awareness over who may eventually have access to an individual's DNA data after a sample is submitted through an at-home genealogy company. The U.S. lacks federal regulations specific to third party aggregation and the sale of genetic data.

"In the U.S., your HIPAA law allows you to have protection based upon what's called covered providers, your health care company or your health care provider, but not third-party aggregators or collectors of data like genetics [providers]," Evanina said.

Anne Wojcicki, the cofounder and CEO of direct-to-consumer DNA testing firm 23andMe, told 60 Minutes that she believes that her company adheres to stricter security measures than HIPAA requires.

"If I want to provide my customers with the best data security, there's all kinds of standards that are out there that do not involve HIPAA," Wojcicki said. "We have an incredibly sophisticated, nimble team that thinks all day long about data security, privacy, how do we make sure that we are doing everything reasonably possible to protect our customers' data."

In 2018, 23andMe began a partnership with the pharmaceutical company GlaxoSmithKline to develop medicines based on human genetic information. Wojcicki said that her company never defaults its customers into the database the firm uses for research, but that 80% of 23andMe's clients have opted in.

"If you talk to anyone who is sick, especially anyone with a terminal illness and you ask them what they want, what they're looking for is a treatment or something that's going to benefit their children," Wojcicki said to Wertheim. "And we learned the most important thing that 23andMe could do would be to put our own money into developing ways our customers are going to benefit from the human genome. But I should emphasize we are reinvesting all of our money into therapeutics development."

True to her promise of using the company's technology for the public good, last week, 23andMe launched an interactive tool that the company says, "allows people to see how certain non-genetic factors may impact the risk for hospitalization due to the [COVID-19] virus." On its website, the company says the tool was created using data from at least 10,000 people who enrolled in the study and provided saliva samples.

These samples may help advance scientific understanding of COVID-19, while also illustrating the potential that lies in large troves of DNA data, built on a foundation laid by scientists Watson and Crick nearly seven decades ago.

The videos above were produced by Keith Zubrow and Sarah Shafer Prediger. They were edited by Sarah Shafer Prediger.

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The risks and rewards of at-home genealogy testing - CBS News

Dogs have been following humans for thousands of years.

Archaeological and genetic data has revealed that dogs accompanied humans when they were migrating to the Americas from East Asia, according to a study published Monday in the Proceedings of the National Academy of Sciences.

Dogs were likely domesticated over 23,000 years ago in Siberia, said lead study author and archaeologist Angela Perri, a research fellow at Durham University's department of archaeology in the United Kingdom. Her team analyzed the genetic makeup of ancient dog remains to estimate when the domestication from wolves to dogs happened.

Archaeological evidence showed that the humans migrated over 15,000 years ago from Northeast Asia across the Bering Land Bridge, a piece of land that connected modern-day Russia to Alaska. The land crossing no longer exists due to rising sea levels.

Perri studied the lineage of American dogs outside the Arctic, which come from a different genetic ancestor than Arctic dogs, and traced it back to ancient Siberian dogs. This lineage has shown that humans brought their dogs with them when they migrated to the Americas, according to the study.

Many people have dogs as pets today and some wonder, "What is this animal and how did it go from a wild predator to curled up next to my bed?" Perri noted.

While there is no definitive answer on why dogs became domesticated, the freezing climactic conditions during this time likely brought wolves and humans closer together for survival, she said.

"Wolves likely learned that scavenging from humans regularly was an easy free meal, while humans allowed this to happen so long as wolves were not aggressive or threatening," Perri said.

The dogs could have also helped humans transport items faster, she said. There is also evidence in the Pacific Northwest of humans using furry creatures as emergency sources of food and fur.

The study is a fascinating example of how canine and human DNA and archaeology can be used to find out more about our past, said Jeffrey Kidd, associate professor of human genetics at the University of Michigan Medical School, who was not involved in the study.

Modern dogs are similar to domesticated dogs from 15,000 years ago, he said, but today there are different furs and colors as a result of breeding.

Kidd is not surprised that humans brought their dogs with them when they migrated to the Americas because of how intertwined dogs are in our society.

"If you and your entire community was going on a journey across the land, wouldn't you bring along your dog?" Kidd said.

The earliest confirmed dog bones were found in Germany over 100 years ago and are about 15,000 years old, Perri said, so her next project is to search for older dog bones in Siberia to aid in her research. She's hoping to gather more evidence to discover how dogs became man's best friend.

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Dogs likely migrated to the Americas with humans over 15,000 years ago, study says - WAAY

Getting old is a complex matter. Research has shown that gut microbes are one of the factors that can influence several aspects of human life, including aging. Elucidating how a specific microbial species contributes to longevity is quite challenging given the complexity and heterogeneity of the human gut environment.

To explore the influence of bacterial products on the aging process, researchers at Baylor College of Medicine and Rice University developed a method that uses light to directly control specific gene expression and metabolite production from bacteria residing in the gut of the laboratory worm Caenorhabditis elegans.

We used optogenetics, a method that combines light and genetically engineered light-sensitive proteins to regulate molecular events in a targeted manner in living cells or organisms, said co-corresponding author Dr. Meng Wang, Robert C. Fyfe Endowed Chair on Aging and professor of molecular and human genetics and the Huffington Center on Aging at Baylor.

In the current work, the team engineered E. coli bacteria to produce the pro-longevity compound colanic acid in response to green light and switch off its production in red light. They discovered that shining the green light on the transparent worms carrying the modified E. coli induced the bacteria to produce colanic acid, which protected the worms gut cells against stress-induced mitochondrial fragmentation. Mitochondria have been increasingly recognized as important players in the aging process.

When exposed to green light, worms carrying this E. coli strain also lived longer. The stronger the light, the longer the lifespan, said Wang, an investigator at Howard Hughes Medical Institute and member of Baylors Dan L Duncan Comprehensive Cancer Center. Optogenetics offers a direct way to manipulate gut bacterial metabolism in a temporally, quantitatively and spatially controlled manner and enhance host fitness.

For instance, this work suggests that we could engineer gut bacteria to secrete more colanic acid to combat age-related health issues, said co-corresponding author Dr. Jeffrey Tabor, associate professor of bioengineering and biosciences at Rice University. Researchers also can use this optogenetic method to unravel other mechanisms by which microbial metabolism drives host physiological changes and influences health and disease.

Read the complete report in the journal eLife.

Other contributors to this work include first author Lucas A. Hartsough, Mooncheol Park, Matthew V. Kotlajich, John Tyler Lazar, Bing Han, Chih-Chun J. Lin, Elena Musteata and Lauren Gambill. The authors are affiliated with one of more of the following institutions: Baylor College of Medicine, Rice University and Howard Hughes Medical Institute.

Funding for this project was provided by Human Health Services and National Institutes of Health grants (1R21NS099870-01, DP1DK113644 and R01AT009050), National Aeronautics and Space Administration (grant NSTRF NNX11AN39H), the John S. Dunn Foundation and the Welch Foundation.

By Ana Mara Rodrguez, Ph.D.

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Light-activated genes illuminate the role of gut microbes in longevity - Baylor College of Medicine News

Dr. Li has over 30 years of experience in basic and applied biomedical research. She joins Neurophth from the University of Louisville School of Medicine, where she was a professor in the department of Ophthalmology and Visual Sciences for over 14 years. Her research focuses on the role of Hippo/YAP1 signaling pathway on different stages of ocular development, NF-kB/IKK2 inhibition of neovascularization, and gene discovery screening for eye diseases using mouse models.

Throughout her career, Dr. Li has contributed to more than 45 publications in journals including Investigative Ophthalmology & Visual Science (IOVS), Proceedings of the National Academy of Sciences of the United States of America(PNAS), Nature Review Immunology, and Science. She is currently the editorial board member of Scientific Reportsand Source Journal of Ophthalmology. Dr. Li holds a Ph.D. in cell biology from the Washington University in St. Louis and obtained both her Bachelor's and Master of Science degrees in Genetics from Beijing University.

"We are thrilled to have Dr. Li on our team, bringing over 3 decades of her diverse experience in basic and applied biomedical research," said Bin Li, M.D., Ph.D., Founder and Chairman of the Board of Neurophth. "Given her prior experience at Baylor College of Medicine mentored by Dr. Savio Woo, an internationally recognized expert in molecular human genetics and gene therapy, and Dr. Mark Kay, a leading researcher in the fields of AAV gene therapy and the current Head of Division of Human Gene Therapy at the Stanford University School of Medicine, Dr. Li has extensive knowledge in gene therapy for hepatic deficiencies, ocular diseases, and viral vector reconstruction."

"We are excited to have Qiutang join and expand our exceptional research and development team. She brings a wealth of experience in gene therapies for ocular diseases to Neurophth," said Alvin Luk, Ph.D., M.B.A., C.C.R.A., Chief Executive Officer at Neurophth. "Her deep understanding of viral vector design and animal models in the inhibition of neovascularization for ocular diseases, such as age-related macular degeneration and diabetic retinopathy, further bolsters our ability to deliver on our growing pipeline of clinical programs and platform capabilities."

"It has been captivating to watch the scale, scope, and speed with which Neurophth has successfully transformed itself into an innovative and diversified gene therapy company," said Dr. Li. "I look forward to being a part of Neurophth team as the company executes the next stage of its growth strategy and expands its pipeline of gene therapy candidates focused on ocular and non-ocular diseases, building a brighter future for patients worldwide."

About Neurophth

Neurophth is China's first gene therapy company in ophthalmic diseases.Headquartered in Wuhan with subsidiaries in Shanghai, Suzhou, and the U.S., Neurophth, a fully integrated company, is striving to discover and develop gene therapies for patients suffering from blindness and other eye diseases globally. Our AAV validated platform which has been published in Nature - Scientific Reports, Ophthalmology, and EBioMedicine, successfully delivered proof-of-concept data with investigational gene therapies in the retina. Our most advanced investigational candidate, NR082 (rAAV2-ND4), in development for the treatment ofND4-mutated LHON, has received orphan drug designations in theU.S. The pipeline also includesND1-mutated LHON, autosomal dominant optic atrophy, glaucoma, wAMD/DME, and other preclinical candidates. Neurophth has initiated the scaling up in-house process in single-use manufacturing technologies to support future commercial demand at the Suzhou facility. To learn more about us and our growing pipeline, visitwww.neurophth.com.

SOURCE Neurophth Therapeutics, Inc.

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Neurophth Therapeutics Further Expands Ocular Gene Therapy Expertise with Appointment of Qiutang Li, Ph.D., as Chief Scientific Officer - PRNewswire

Researchers at Weill Cornell Medicine and Cornell Universitys Ithaca campus have developed a new computational method for studying genetic and environmental interactions and how they influence disease risk.

Theresearch, in The American Journal of Human Genetics, makes the process of finding these interactions much less difficult and demonstrates their importance in determining body mass index and diabetes risk.

Our study demonstrates that your genes matter and the environment matters and that the interaction of the two can increase risk for disease, said co-senior author,Dr. Olivier Elemento, who is professor of computational genomics in computational biomedicine, professor of physiology and biophysics, associate director of the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, and director of the Caryl and Israel Englander Institute for Precision Medicine at Weill Cornell Medicine.

Typically, studying gene-environment interactions creates a huge computational challenge, said lead author Andrew Marderstein, a doctoral candidate in the Weill Cornell Graduate School of Medical Sciences whose research was conducted both in Dr. Elementos lab in New York City andDr. Andrew Clarkslab in Ithaca, enabling him to have immediate access to computational biology and population health expertise.

Genotype-environment interaction can be thought of as the situation where some genotypes are much more sensitive to environmental insults than others, said Dr. Clark, co-senior author and Jacob Gould Schurman Professor of Population Genetics in the Department of Molecular Biology and Genetics in the College of Arts & Sciences and a Nancy and Peter Meinig Family Investigator at Cornell University. These are exactly the cases where changes in the diet or other exposures might have the biggest improvement in health, but only for a subset of individuals.

The millions of genetic variants, or inherited genetic differences found between individuals in a population, and different lifestyle and environmental factors, such as smoking, exercise, different eating habits, can be analyzed for combined effects in numerous ways. When researchers test for gene-environment interactions, they typically analyze millions of data points in a pairwise fashion, meaning they assess one genetic variant and its interaction with one environmental factor at a time. This type of analysis can become quite labor intensive, said Marderstein.

The new computational method prioritizes and assesses a smaller number ofvariantsin the genomeor the complete set of genetic material found in the bodyfor gene-environment interactions.We condensed a problem withanalyzing10 million different geneticvariantsto essentiallyanalyzing only tens ofvariants indifferent regions of the genome, Marderstein said.

While a standard genetic association study might look at whether asinglegeneticvariantcould lead to an average change in body mass index (BMI), this study assessed which geneticvariantswere associated with individuals being more likely to have a higher BMI or lower BMI. The researchers found that looking for sections of DNA associated with the variance in a human characteristic, called a variance quantitative trait locusor vQTL, enabled them to more readily identify gene-environment interactions. Notably, thevQTLs associated with body mass index were also more likely to be associated with diseases that have large environmental influences.

Another area of study where the new computational method might useful is determining how an individual might respond to a specific drug based on gene-environment interactions, said Marderstein. Analysis of social determinants of health, meaning a persons environmental and social conditions, such as poverty level and educational attainment, is a third area that the researchers are interesting in pursuing, according to Dr. Elemento.

Overall, scientists in the precision medicine field are realizing they can sequence a persons DNA, in addition to assessing environmental factors such air quality and physical activity, to better understand whether the individual is at risk of developing a specific disease. The idea down the line is to use these concepts in the clinic, said Dr. Elemento. This is part of the evolution of precision medicine, where we can now sequence somebody's genome very easily and then potentially analyze all of the variants in the genetic landscape that correlate with the risk of developing particular conditions.

Reference: Marderstein AR, Davenport ER, Kulm S, Van Hout CV, Elemento O, Clark AG. Leveraging phenotypic variability to identify genetic interactions in human phenotypes. AJHG. 2021;108(1):49-67. doi:10.1016/j.ajhg.2020.11.016.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Simplifying the Study of Gene-Environment Interactions - Technology Networks

THOUSAND OAKS, Calif., Jan. 28, 2021 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that it will report its fourth quarter and full year 2020 financial results on Tuesday, Feb. 2, 2021, after the close of the U.S. financial markets. The announcement will be followed by a conference call with the investment community at 5 p.m. EST. Participating in the call from Amgen will be Robert A. Bradway, chairman and chief executive officer, and other members of Amgen's senior management team.

Live audio of the conference call will be simultaneously broadcast over the internet and will be available to members of the news media, investors and the general public.

The webcast, as with other selected presentations regarding developments in Amgen's business given by management at certain investor and medical conferences, can be found on Amgen's website, http://www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen's Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

About AmgenAmgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to beone ofthe world'sleadingindependent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visitwww.amgen.comand follow us onwww.twitter.com/amgen.

CONTACT: Amgen, Thousand OaksMegan Fox, 805-447-1423 (media)Trish Rowland, 805-447-5631(media)Arvind Sood, 805-447-1060 (investors)

View original content to download multimedia:http://www.prnewswire.com/news-releases/amgen-announces-webcast-of-2020-fourth-quarter-and-full-year-financial-results-301217691.html

SOURCE Amgen

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Amgen Announces Webcast Of 2020 Fourth Quarter And Full Year Financial Results - BioSpace

There are so many different companies that offer genetic analysis to any interested client. One such company, 23andMe, offers some interesting features for those who use itsservices.

It provides insight into a users ethnic history and even breaks down parts of their genetic codes to explain how DNA influenced their appearance or senses. In addition to these easy-to-understand hereditary summaries, it also gives clients a copy of their "raw data."

Here, we'llgo over whattools you can use to interpret your 23andMe raw data, and we'll define what exactly raw data is.

To understand raw data, you need to know a little bit about how DNA works. DNA is something we inherit from both of our parents and, subsequentially, all previous ancestors. Unless you have an identical twin, your genetic code is unique to you. Understanding what your "genetic code" is can help you learn about raw data.

Deoxyribonucleic Acid (DNA) is a molecule that dictates everything that makes us, us. It contains codes for everything from our basic biology to personalized features. While all humans share a majority of the sequence, humans experience small differences in base pairs, which may influence everything, such as our appearance, behavior, and predisposition to diseases.

Base pairs are the "building blocks" of our genetic makeup. When looking at a model of a DNA double helix, they are those little "steps" of the ladder. Each step is comprised of one of four bases: adenine (A), cytosine (C), guanine (G), or thymine (T), and its complementary base pair (A and T or G and C).

When you send your tissue sample over to 23andMe facilities, scientists perform a process called genotyping. As opposed to sequencing, where technicians attempt to calculate the exact sequence of a given length of DNA, genotyping offers an accurate (and cost-effective) shortcut.

Our genetic code is very long, and there are huge chunks of information we cant do anything with yet. Genotyping is a far more effective process for getting useful data for clients.

The process scans genetic code to look for specific gene variants that are very popular or ones that we already know about. 23andMe takes these datasets and transforms them into an easy-to-understand infographic.

What you'll see is a neat little printout letting you know where your ancestors originated from. What the scientists behind the scenes see is a printout containing various locations and a whole bunch of As, Gs, Ts, and Cs. This printout is your raw data that 23andMe sends you with your results.

Related:The Best Ancestry Tracing Sites

Your raw data may seem like a jumbled mess of characters, but its incredibly useful information. Although 23andMe offers some insight into the genetic information it analyzes, it doesn'texplain everything.

The raw data offers tons of surprise information that you can use. This information isnt just interesting from ahistoricalperspective; the information also offers insight into your health and can be a useful genealogy tool for you and your loved ones.

To access this information, you need to find how to "read" this information. Luckily, you dont need to be a renowned geneticist to take that raw data and do something with it.

While you could theoretically search through journals and try to analyze your raw data yourself, there are a couple hundred thousand markers to sift through. The best way to make the most out of your raw data is to utilize one of the many available tools online.

With countless platforms to chose from, it may be challenging to pick out the best one for you. Consider what information you want to learn from your raw data before you choose an analysis tool.

Xcode Life offers a variety of packages, so you can order exactly what you want. With many different reports to chose from, you can customize the information you want, as well as find options to fit your budget. It displays its findings in an easy-to-read format for everyone to enjoy.

There are over 15 options to choose from, including Gene Sleep, Traits and Personality,Gene Allergy, and more.There are also different bundles available so you can save money. Its packages start at $20.

If you are interested in finding extended ancestry information and basic health information, DNA Land offers free assessment packages.

Although it doesn'tgo into as much detail as some of the paid contenders, it offers great added insight at no extra charge. DNA Land will even use your anonymous submissions to further scientific research.

Nutrahacker takes gene analysis one step further. It designs your reports so that you can "empower yourself" with the newfound information.

Its specialized assessments determine an optimized list of supplements and fitness information for you, in addition to general health data. While its packages start at $25, it also offers some free basic assessments.

If you are on a tighter budget, Promethease offers more inexpensive health reports. It anonymously cross-references your raw data with SNPedia, a human genetics wiki. While it gives you a lot of information for the price, the process is not as straightforward as other options.

You dont need to be an expert, but many find the platform a bit more technical. However, having a super basic background in statistics should suffice. Health reports start at $12.

Research continues to advance every day, and Genomelink makes a point to keep its dynamic options updated by the week. It offers over 200 analysis options to investigate everything from your personality and career strengths to your health vulnerabilities and longevity.

If you're on a budget, Genomelink also has over 20 free analyses. These come with the option to order premium reports delivered via straightforward infographics.

There is so much information to learn from your genetic makeup. With so many easy and accessible tools to further explore the data you already paid for, why not make the most of what you have? It only takes a few clicks of a button to receive a comprehensive health report that is both interesting and informative.

Considering online DNA testing? Several options are available, but 23andMe and ancestryDNA are the top dogs.

Brittni is a neuroscience graduate student who writes for MakeUseOf on the side of her studies. Shes a seasoned writer who began her freelance writing career back in 2012. While shes mainly focused on technology and medicine shes also spent time writing about animals, pop culture, video game recommendations, and comic book reviews.

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Turn 23andMe Raw Data Into Meaningful Results With These Websites and Tools - MakeUseOf

Introduction

Calcium channel blockers (CCBs) are widely used in the treatment of hypertension. In addition to their antihypertensive effects, CCBs may also lead to many adverse reactions, including peripheral edema, dizziness, flushing, fatigue, headache, palpitations, and gingival enlargement.14 Peripheral edema, particularly of lower limbs, is the most common side effect of CCBs. CCBs-induced peripheral edema is more common in women and is related to age, upright posture and duration of CCBs therapy.2,5 Although it has been known for decades that CCBs could cause peripheral edema, there are still very few genetic markers that could be used in clinical treatment.

Amlodipine is a first-line antihypertensive drug and a long-acting 1,4-dihydropyridine calcium channel blocker.6 It became the fifth most prescribed medication in the United States in 2018.7 However, therapy trials report that the incidence of amlodipine-induced peripheral edema is about 19%, which also probably serves as the main reason behind the limited use of this drug.8,9 To our knowledge, factors that increase the serum concentration of drugs may also increase the risk of side effect. Accordingly, genetic factors affecting the metabolism of amlodipine will consequently influence its clearance, thus possibly resulting in peripheral edema. In recent years, numerous studies have focused on identifying genetic factors determining the responses to amlodipine therapy, including aspects of efficacy and safety.1012 Nevertheless, the genetic predisposition to amlodipine-induced peripheral edema remains unclear. However, some studies shine light on CYP genes, which are involved in the metabolism of amlodipine.13,14

CYP3A is a subfamily of cytochrome P450 and is involved in the metabolism of many compounds.10,1517 CYP3A4 and CYP3A5 are the two major enzymes of CYP3A family and play important roles in the dehydrogenation of amlodipine.18 However, it has been reported that CYP3A4, rather than CYP3A5, plays a more important role in amlodipine clearance in vivo.16 However, according to our observations, almost all SNPs of CYP3A4 are very rare in Chinese Han or East Asian.1921 A recent study evaluated the influence of CYP3A polymorphisms on the pharmacokinetic (PK) parameters of 10 CYP3A substrates including amlodipine, and it turned out CYP3A4 polymorphisms did not show a pronounced influence on PK of amlodipine.22 So, as far as we know, CYP3A4 does not suffice as an explanation towards the incidence of amlodipine-induced adverse responses. Additionally, the contribution of CYP3A5 in amlodipine metabolism is still controversial. CYP3A5 expression varies among individuals due to gene polymorphisms that result in non-productive mRNA splicing and lower or undetectable expression of the protein.14,23,24 Pharmacogenomics studies have found that CYP3A5 gene polymorphisms have significant impact on drug metabolism, efficacy, and toxicity.25,26 Recent studies have reported a possible relationship between CYP3A5 and amlodipine. CYP3A5*3/*3 genotypes might be associated with blood pressure response to amlodipine,27 and CYP3A5*3 may affect the disposition of amlodipine.13 In Chinese hypertensive patients who underwent renal transplantation, researchers have demonstrated that CYP3A5*3 polymorphism affects the antihypertensive efficacy of amlodipine. In such patients with CYP3A5*3/*3, the reduction in diastolic blood pressure (DBP) was significantly higher than those with other genotypes.28 Additionally, compared with CYP3A5*1/*1, CYP3A5*1/*3 patients exhibit a lower metabolic ratio of amlodipine in vivo and hypertensive patients with CYP3A5*1/*3 genotypes show a higher decrease in blood pressure.14 These findings suggest that CYP3A5 genetic variants are really involved in amlodipine response, having an impact on treatment effectivity of amlodipine.

Although studies have identified that CYP3A5 polymorphisms do play a role in blood pressure control and treatment responses of amlodipine, the effect of a particular genotype in amlodipine-induced peripheral edema remains unclear. Here, we aim to test whether any genetic variants associate with amlodipine-induced peripheral edema. For this, we used the targeted region sequencing method to genotype the SNPs in all known haplotypes of CYP3A5, and evaluated their effect on amlodipine-induced peripheral edema in Chinese Han hypertensive patients.

We recruited a total of 240 patients with essential hypertension who have ever been treated with amlodipine or L-amlodipine for more than 4 weeks. The participants were outpatients from Beijing Chaoyang Hospital of Capital Medical University and the Second Hospital of Jilin University. The demographic characteristics and baseline data were collected, including gender, age, body mass index (BMI), smoking and drinking status, blood pressure, heart rate and use of medications. Participants were also questioned about peripheral edema symptoms (leg or ankle edema). Two trained physicians evaluated the adverse drug reactions caused by the amlodipine or L-amlodipine based on the WHO-UMC scale.29 We classified the participant as a peripheral edema case if WHO-UMC causality categories were certain, probable, or possible. The others were grouped as controls.

The DNA Sampling Swabs (Taitong Gene Testing Equipments Co., Ltd., Suzhou, China) were used for collecting oral buccal mucosa cells. Genomic DNA was isolated from the swabs, using Hi-Swab DNA kit (TIANGEN, Beijing, China) according to the manufacturers instructions. Quantification of the DNA concentration was performed using the manufacturers protocol with the Qubit dsDNA HS Assay Kit (Yeasen, Shanghai, China). Methods for targeted region capture and NGS have been reported previously.30 Illumina HiSeq X was used to sequence the captured DNA with paired-end reads of 150 bp length. Table S1 lists the targeted regions of sequencing and the 24 SNPs of CYP3A5.

High-quality sequencing reads were obtained from the raw data by removing reads that contained adapters, were with unknown bases, or had a low-quality using the Trimmomatic (v0.36)31 program. The high-quality reads were aligned to human reference genome hg19 using the Burrows-Wheeler Aligner (BWA, v0.7.15)32 using the default parameters. The Genome Analysis ToolKit (GATK, v3.8)33 was used for indels realignment, quality score recalibration, variant calling, and genotyping (using Haplotype Caller).

Demographic and clinical characteristics of different groups were compared by t-test or Chi-square (2) test according to the data category. The associations between gene polymorphisms and the risk of peripheral edema were assessed by codominant model, dominant model, recessive model and allele model by calculating the odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression with or without adjustment by gender and alcohol status. Stratification was done by gender. Analyses above were carried out on R-4.03. PLINK 1.934 was used to calculate the minor allele frequency and assess HardyWeinberg equilibrium (HWE) for each SNP. Additionally, linkage disequilibrium (LD) block and haplotype were assessed by Haploview35 software. The D and r2 values for all pairs of SNPs were calculated. P value<0.05 was considered as the significant level.

Two hundred and forty enrolled patients were separated into 64 cases and 176 controls. The general characteristics of the study population are summarized in Table 1. In agreement with previous reports, a higher incidence of CCB-induced peripheral edema was observed in women. A significant difference was found in the sex ratio between cases and controls (P=0.00048). In addition, the frequency of drinkers was 29.69% in the case group and 46.02% in the control group (P=0.034). There was no significant difference between the two groups regarding other characteristics.

Table 1 Characteristics of the Study Population

All the observed SNPs and the minor allele frequencies (MAF) in two groups are listed in Table 2. Except rs15524, rs4646453 and rs776746, the other SNPs were rare or not detected in the studied population. Therefore, we focused on these three SNPs (MAF>0.05) for further studies. Distributions of genotype frequencies of the SNPs did not show any deviation in HardyWeinberg equilibrium (P>0.05).

Table 2 Observed CYP3A5 Variations and Frequencies

The genotype and allele allocations of the test polymorphisms differed considerably between cases and controls (Table 3). In more detail, the frequencies of alleles rs15524 G, rs4646453 A, and rs776746 T were significantly lower in cases than those in the control group (G vs A: OR=0.53, P=0.011; A vs C: OR=0.54, P=0.019; T vs C: OR=0.58, P=0.03; respectively). Furthermore, there was a statistically significant difference in genotype of the rs15524 and rs4646453 between the two groups in dominant model with or without adjustment by gender and alcohol status (GG+AA vs AA: OR=0.5, P=0.021; AA+AC vs CC: OR=0.54, P=0.04). As for rs776746, the presence of TT+CT genotype demonstrated a significantly lower risk after gender and alcohol status adjustment (TT+CT vs CC: OR=0.57, adjusted P=0.044).

Table 3 Genotype Frequencies of Study SNPs in Case and Control Groups

Stratified analyses were performed to access the differential effect of gender on the association between amlodipine-induced edema and the polymorphisms. No significant differences were identified, but the relevant genotypes still showed lower risk in all subgroups. The details are presented in Table 4.

Table 4 Stratified Analyses Between SNPs and Risk of Amlodipine-Induced Peripheral Edema

We employed Haploview program to assess the Linkage disequilibrium (LD) block and haplotype of the three SNPs of CYP3A5. The LD analysis indicated that these SNPs were in strong LD with each other (Figure 1, rs15524 and rs4646453 D=0.965, r2=0.821; rs15524 and rs776746 D=0.979, r2=0.919; rs776746 and rs4646453 D=0.989, r2=0.898). Frequencies of four haplotypes were found to be more than 1% in the haplotype analysis (Table 5). The most represented haplotype in the whole cohort of controls and cases was ACC, followed by GAT, GCC and GCT. Two haplotypes (ACC and GAT) were significantly associated with the risk of amlodipine-induced peripheral edema. The frequency of the ACC haplotype was higher in the cases than controls (79.7% vs 67.9%, P=0.012), whereas the frequency of the GAT haplotype was lower in the cases (17.2% vs 28.1%, P=0.015).

Figure 1 Linkage disequilibrium coefficients (|D|) and LD block among the three polymorphisms of CYP3A5.

Table 5 Haplotype Frequencies of CYP3A5 Gene and the Association with the Amlodipine-Induced Peripheral Edema Risk

Studies have demonstrated that genetic polymorphisms may influence the gene function, thus causing alterations in the pharmacokinetics (PK) and pharmacodynamics (PD) of the gene-associated drugs. Moreover, genetic variants have been confirmed for their association with appearance of adverse reactions to drugs, such as ACE inhibitors-induced cough36 and rosuvastatin-induced myotoxicity.37 To our knowledge, this is the first study to investigate the relationships of CYP3A5 polymorphisms and amlodipine-induced peripheral edema by using a casecontrol retrospective study in the Chinese population. Our study reveals that amlodipine-induced peripheral edema may associate with genetic polymorphisms in CYP3A5 gene. We find that the distribution of allele and genotype frequencies of the three SNPs are significantly different between cases and controls. Specifically, the alleles rs15524 G, rs4646453 A, and rs776746 T reduce the risk of amlodipine-induced peripheral edema. On the other hand, A, C, and C increase the risk and haplotype analysis also confirms this. These findings support the hypothesis that genetic variation in CYP3A5 is involved in the development of amlodipine-induced peripheral edema.

CYP3A5 is highly polymorphic with significant inter-individual variation in the enzyme activity contributing to the absorption, metabolism and tissue distribution of drugs.24,38 Genetic polymorphisms of CYP3A5 may potentially alter its proteins expression and function, and subsequently influence the clearance of any drugs metabolized by CYP3A5.38 The most studied SNP related to CYP3A5 functional variation is rs776746 (also known as CYP3A5*3 or CYP3A5*3C). Homozygous carriers of this SNP (*3/*3 or CC) lack functional CYP3A5 protein because of the frameshift mutation and truncation of the translated protein.39 Previous studies have confirmed that CYP3A5*3 is associated with drug metabolism, and CYP3A5*3/*3 carriers have decreased metabolism of nifedipine40 and tacrolimus,41 compared to CYP3A5*1/*1 and CYP3A5*1/*3 carriers. Patients with CYP3A5*3/*3 who are treated with tacrolimus may have an increased risk of nephrotoxicity as compared to patients without it.25,26 These findings suggest that the CYP3A5 *3/*3 carriers have low activity of CYP3A5 enzyme and decreased metabolism for certain drugs dependent on it, resulting in the appearance of an adverse reaction to the drug. Conforming to these findings, our study also indicates that there is an association between CYP3A5*3 and the occurrence of amlodipine-induced peripheral edema and that *3/*3 (CC) carriers have a higher risk of peripheral edema.

CYP3A5*1D (rs15524) is another frequently studied SNP in CYP3A5, which is in the 3-untranslated region (UTR). CYP3A5*1D is differentially distributed among populations ranging from 77.5% in Americans to 71.4% in East Asians, 40.6% in Africans, and even rarer in Europeans (less than 8%) (GnomAD).21 SNPs in UTRs may influence the stability of mRNA, thus affecting the expression and activity of the enzyme.42,43 According to a study identifying the potential SNPs related to miRNA, rs15524 may influence the hsa-miR-500a-5p that targets CYP3A5, affecting its expression.44 In addition, studies have found that CYP3A5*1D influences the pharmacokinetics of many drugs, including tacrolimus45 and carbamazepine.46 Therefore, rs15524 may act as a genetic marker and should be considered while studying or prescribing drugs metabolized by CYP3A5. Here, we find that the frequencies of rs15524 G allele and GA+GG genotypes in cases are lower than controls, which indicates that this SNP is associated with reduced risk of incidence of amlodipine-induced peripheral edema. In other words, CYP3A5*1D/*1D carriers may have an increased risk than others.

As for CYP3A5*1E (rs4646453), it is associated with a decreasing risk of amlodipine-induced peripheral edema. However, there is litter information about the function of the rs4646453. To some extent, this is possible because the SNP locates in the intron region. Studies have revealed that CYP3A5 rs4646453 is in LD with rs776746,47 and there is a strong LD between rs15524 and rs776746.39,46 Our findings are consistent with these studies and further promote that the presence of LDs with rs776746 may partly explain the role of rs15524 and rs4646453 in amlodipine-induced peripheral edema.

Given all these findings, there are some limitations in our present study that we would like to acknowledge. First, the population in our study is Chinese Han, and it is known that the frequency of mutations differs among ethnic groups. Hence, our results may apply well to Chinese population but are probably not suitable for populations of other ethnic groups. Second, we have performed a retrospective study and not a prospective one. The study is also limited by the smaller number of samples. The third limitation is not involving other genes contributing to amlodipine metabolism, such as CYP3A4. As we mentioned before, polymorphisms of CYP3A4 are rare in Chinese, and the evidence so far that CYP3A4 polymorphisms influence amlodipine metabolism is scarce. So, we took no account of them currently. But it would be better for future studies to include these related genes to better explain the connection between genetic factors and amlodipine-induced peripheral edema. Hence, more casecontrol studies with large number of polyethnic samples and involvement of diversified factors are necessary.

None the less, our study does investigate the novel relationship between the genetic variants and amlodipine-induced peripheral edema. In conclusion, we provide evidence that CYP3A5 polymorphisms are involved in the occurrence of amlodipine-induced peripheral edema, and the three genetic variants of CYP3A5 have the potential to serve as novel biomarkers for amlodipine-induced adverse reactions. Our findings thus provide new insights into amlodipine-induced peripheral edema and are of importance in developing and prescribing personalized and precise medicine for hypertension.

The raw data are available on reasonable request to the correspondence author Songnian Hu.

All the participants have signed the written informed consent, and approval was obtained from the Research Ethics Board of Beijing Chaoyang Hospital of Capital Medical University and the Research Ethics Board of the Second Hospital of Jilin University. This study has been conducted in accordance with the World Medical Association Declaration of Helsinki.

We thank all the participants included in this study.

All authors declare that they have no conflicts of interest for this work.

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[Full text] Association of CYP3A5 Gene Polymorphisms and Amlodipine-Induced Periph | PGPM - Dove Medical Press