Category Archives: Transhuman News

April 2, 2017 3D chemical structure of bisphenol A. Credit: Edgar181 via Wikimedia Commons

Exposure during infancy to the common plasticizer bisphenol A (BPA) "hijacks" and reprograms genes in the liver of newborn rats, leading to nonalcoholic fatty liver disease (NAFLD) in adulthood. A new study has found how this process occurs, and researchers will present the results Saturday at ENDO 2017, the Endocrine Society's 99th annual meeting in Orlando, Fla.

NAFLD is a buildup of extra fat in liver cells that is not caused by alcohol and that can lead to cirrhosis, or scarring, of the liver. This common disease occurs more often in people with obesity, diabetes, high cholesterol or high triglycerides (blood fats).

BPA is an industrial chemical found in polycarbonate plastics, such as many food and beverage containers, and in epoxy resins that line food cans. Past studies show that BPA and many other chemicals in our environment are endocrine-disrupting chemicals that can interfere with the body's hormones and eventually lead to obesity and other diseases.

"We believe this disease risk occurs via developmental reprogramming of the epigenome, which can persist throughout a lifetime," said the study's lead investigator, Lindsey Trevio, Ph.D., an instructor and researcher at Baylor College of Medicine, Houston, Texas. "These persistent changes lead to alterations in gene expression in ways that correlate with increased disease susceptibility."

In both rats and humans, the epigenome programs our complete set of DNA (the genome), but unlike genetic defects, epigenomic reprogramming can be reversed, Trevio said.

"Understanding the mechanisms underlying this endocrine disruptor-mediated epigenomic reprogramming may lead to the identification of biomarkers for people at risk as well as possible interventions and therapeutics for NAFLD," she said.

In research funded by the National Institute of Environmental Health Sciences, Trevio and her colleagues sought to identify the molecular causes of the developmental reprogramming they had observed in past animal studies. They treated newborn rats with low, environmentally relevant doses of BPA during a critical period of liver development: the five days after birth. The liver, she explained, is "a central player in fat metabolism and obesity." Then they examined liver tissue from the BPA-exposed rats immediately after exposure or when the rats were adults. These tissue samples were compared with liver samples from control rats who did not receive BPA.

Trevio reported that BPA-exposed rats, but not control rats, that were fed a high-fat diet as adults had increased liver weight and raised levels of total cholesterol, "bad" (LDL) cholesterol and triglycerides. Furthermore, genes involved in the progression of NAFLD exhibited increased expression in the liver of the BPA-exposed rats, but not in control animals. Specifically, she said they found that BPA created two new activating epigenomic marks on genes driving progression of NAFLD. These marks appear at key regulatory regions of affected genes, thus likely becoming "super promoters" that code the gene to turn on. However, she noted that this change appears to require a later-in-life challenge, such as eating a high-fat diet.

The researchers have reportedly seen BPA and other endocrine disruptors promoting epigenomic reprogramming in additional tissues in rats. Trevio said, "Our findings could be useful in other diseases as well. Because these endocrine disruptors are ubiquitous in the environment, a large portion of the population may be affected by developmental reprogramming."

Explore further: Endocrine disruptors cause fatty liver

Exposure to low doses of hormone-disrupting chemicals early in life can alter gene expression in the liver as well as liver function, increasing the susceptibility to obesity and other metabolic diseases in adulthood, a new ...

A new study presented today demonstrates that a build-up of fat around the waist can cause more serious complications than obesity in the development of non-alcoholic fatty liver disease (NAFLD). The study was presented at ...

Adult offspring of mothers who used fluoxetine, a common antidepressant, during pregnancy were more likely to develop a fatty liver, a new animal study has found. The results will be reported Saturday at the joint meeting ...

EPFL scientists have discovered a new biological mechanism behind nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world. NAFLD is a frequent finding in patients with type 2 diabetes, but the exact prevalence of NAFLD, as well as whether patients ...

The type of sugar you eatand not just calorie countmay determine your risk for chronic disease. A new study is the first of its kind to compare the effects of two types of sugar on metabolic and vascular function. The ...

Exposure during infancy to the common plasticizer bisphenol A (BPA) "hijacks" and reprograms genes in the liver of newborn rats, leading to nonalcoholic fatty liver disease (NAFLD) in adulthood. A new study has found how ...

Animals can pass the damaging effects of nighttime light exposure to their offspring, a new study has found, adding to a growing body of evidence that there's a health cost to our increasingly illuminated nights.

Northwestern Medicine scientists have identified a novel pathway that regulates cellular iron, which could lead to new therapies for patients with either an overload or deficiency of iron.

Lungs take in oxygen and release carbon dioxide. Yet despite their existential importance, the development of the lungs and the rules governing the process that enables respiration is still not well understood at the molecular ...

Researchers from the European Bioinformatics Institute (EMBL-EBI), University of Cambridge, the Wellcome Trust Sanger Institute and the Cancer Research UK-Cambridge Institute (CRUK-CI) have shed light on a long-standing debate ...

(Medical Xpress)A team of researchers from several institutions in the U.K. and one in the U.S. has developed a faster and cheaper way to figure out which drugs on the market might be useful for treating other ailments. ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Read more here:
Early-life BPA exposure reprograms gene expression linked to fatty liver disease - Medical Xpress

Visit the News Hub

One family with rare gene mutation gives clues to preventing heart attacks

Patients with mutations that disable a gene called ANGPTL3 have extremely low levels of cholesterol in the bloodstream. They also show no evidence of plaque in the coronary arteries, suggesting the mutations protect against heart attacks. Studying such patients can help guide drug development with the goal of preventing heart attacks.

Natural genetic changes can put some people at high risk of certain conditions, such as breast cancer, Alzheimers disease or high blood pressure. But in rare cases, genetic errors also can have the opposite effect, protecting individuals with these helpful genetic mistakes from developing common diseases.

A new study of such beneficial genetic mutations, led by Washington University School of Medicine in St. Louis, may provide guidance on the design of new therapies intended to reduce the risk of heart attacks.

The study is published March 29 in the Journal of the American College of Cardiology.

The researchers studied members of a family with rare mutations in a gene called ANGPTL3. The gene is known to play important roles in processing lipoproteins, molecules that package and transport fat and cholesterol through the bloodstream. Partial or complete loss of this gene was known to cause low cholesterol and triglyceride levels in the bloodstream. But whether it affects risk of heart attack was unclear.

Three of these family members those with a complete loss of this gene showed extremely low blood cholesterol and no evidence of plaque in their coronary arteries. According to the study authors, it was noteworthy that one of these patients showed no evidence of atherosclerosis despite having high risk factors for it, including high blood pressure and a history of type 2 diabetes and tobacco use.

The family members with complete loss of ANGPTL3 have extraordinarily low cholesterol, said first author Nathan O. Stitziel, MD, PhD, an assistant professor of medicine and of genetics. The interesting thing about this family is the individuals with total loss of this gene had siblings with normal copies of the same gene. So we could compare people with differences in the function of this gene who are otherwise closely related genetically and share similar environments. Its an anecdotal study of one family, but we felt it might provide some insight into the effects of blocking ANGPTL3.

While the individuals with nonfunctional copies of the gene showed no coronary plaque, their siblings with working copies of the gene showed evidence of plaque in the coronary arteries, though it was not yet causing symptoms a situation that is common in the general population, according to Stitziel.

To study the gene beyond the experience of a single family, the scientists also analyzed data available from large population studies. In data from one study of about 20,000 patients, the researchers found those with a partial loss of this gene had, on average, 11 percent lower total cholesterol, 12 percent lower LDL cholesterol, and 17 percent lower triglycerides, measured in the blood, than individuals with full gene function.

Analysis of data from other large population studies showed a link between partial loss of the gene and a lower risk of coronary artery disease and an association between lower circulating levels of ANGPTL3 protein and a lower risk of heart attack.

Taken together, these findings provide support for efforts to develop drugs that inhibit ANGPTL3 in order to reduce the risk of coronary artery disease and heart attack. The same reasoning led to the development of a class of drugs known as PCSK9 inhibitors, which have recently been shown to be effective at reducing the risk of heart attack in a large clinical trial of more than 27,000 men and women.

Several years ago, researchers found natural beneficial mutations in the PCSK9 gene that lowered peoples cholesterol levels and protected them from coronary artery disease, much as mutations in ANGPTL3 seem to do. Both PCSK9 and ANGPTL3 are important in the bodys processing of cholesterol from the diet. Any drugs that inhibit them, then, work differently than commonly prescribed statins, which reduce cholesterol levels in the blood by blocking the bodys internal cholesterol manufacturing.

While reducing cholesterol levels in the blood typically is thought to be good for the heart, Stitziel pointed out that there may be dangers to inhibiting the normal function of a gene. Not all genetic mutations that result in low cholesterol in the bloodstream are healthy. For example, there is one genetic disorder in which cholesterol levels in the blood are low because cholesterol gets stuck in the liver, resulting in fatty liver disease.

We need a better understanding of how cholesterol is processed in individuals with complete loss of ANGPTL3 function before we can fully say what effect inhibiting ANGPTL3 is going to have, Stitziel said. Studies of people with mutations that completely knock out a genes function are important because they can provide insight into the potential effects both good and bad of drugs inhibiting that genes function.

Along with Washington University School of Medicine, other institutions that played key roles in the study included the Broad Institute of MIT and Harvard and the Perelman School of Medicine at the University of Pennsylvania.

This study was supported by the National Institutes of Health (NIH), grant numbers R01HL131961, K08HL114642, R01HL118744, R01HL127564, R21HL120781, U54HG003067, UM1HG008895, UM1HG008853, TR001100, T32HL007734, RC2HL101834 and RC1TW008485; the Barnes-Jewish Hospital Foundation; the Fannie Cox Prize for Excellence in Science Teaching, Harvard University; a MGH Research Scholar Award; an ACCF/Merck Cardiovascular Research Fellowship; a John S. Ladue Memorial Fellowship at Harvard Medical School; the BHF and NIHR Senior Investigator support; and Fogarty International, grant number RC1TW008485.

The authors report grant funding or consulting fees from AstraZeneca, Aegerion Pharmaceuticals, Merck, Amarin, Alnylam Pharmaceuticals, Eli Lilly and Company, Pfizer, Sanofi, Novartis, Regeneron, Genentech, Bayer Healthcare, Leerink Partners, Noble Insights, Quest Diagnostics and Genomics PLC. One author, Rader, reports being an inventor on a patent related to lomitapide that is owned by the University of Pennsylvania and licensed to Aegerion Pharmaceuticals. He also reports co-founding Vascular Strategies and Staten Biotechnology. Another author, Kathiresan, reports holding equity in San Therapeutics and Catabasis Pharmaceuticals.

Stitziel NO, Khera AV, Wang X, Bierhals JB, Vourakis C, Sperry AE, Natarajan P, Klarin D, Emdin CA, Zekavat SM, Nomura A, Erdman J, Schunkert H, Samani NJ, Kraus WE, Shah SH, Yu B, Boerwinkle E, Rader DJ, Gupta N, Frossard PM, Rasheed A, Danesh J, Lander ES, Gabriel S, Saleheen D, Musunuru K, Kathiresan S, PROMIS and Myocardial Infarction Genetics Consortium Investigators. ANGPTL3 deficiency and protection against coronary artery disease. Journal of the American College of Cardiology. March 29, 2017.

Washington University School of Medicines 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked seventh in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

Read more:
Genetic errors associated with heart health may guide drug development - Washington University School of Medicine in St. Louis

By Doris T. Zallen | Zallen is professor emerita of science studies and humanities at Virginia Tech. She is the author of To Test or Not to Test: A Guide to Genetic Screening and Risk.

The Preserving Employee Wellness Programs Act (HR 1313), now being pushed by Republicans in the House of Representatives, is a threat to employees, will not improve wellness programs, and has the potential to unleash a corrosive force that could undermine the future of genomic medicine.

Genetic testing is becoming a central tool in the 21st century medical arsenal. Advances in genetics first made it possible to identify specific genes that bring on specific, relatively rare, health conditions such as cystic fibrosis, sickle-cell disease and muscular dystrophy.

Recent advances have yielded genetic tests that can identify people who, though healthy now, are at a higher-than-average risk for developing an illness in the future. Examples here include breast cancer, Parkinsons disease and Alzheimers disease all quite common.

However, these risk-raising genes are imperfect predictors. Environmental factors, including diet and exercise, also play key roles. The reality is that being found to have a risk-raising gene does not mean you will get the disease and, because of the involvement of environmental factors, you can get the disease without having the gene.

HR 1313 would allow employers to require genetic testing of employees in their wellness programs and assess harsh financial penalties on those who refuse. This is bad news. There are perfectly good reasons for people to decide to not have genetic testing for particular genes. Many people, learning of a higher risk for developing a future illness, suffer severe emotional distress, especially when there are no effective treatments or known cures to ward them off.

James Watson, Nobel laureate for the discovery of the structure of DNA, had his entire genome sequenced and made available online to aid in genetic research. But, he insisted that information about one of his own genes, the APOE gene, not be revealed. One form of the APOE gene is a known risk factor for late-onset Alzheimers. He did not want the burden of knowing.

Nancy Wexler, whose pioneering research led to the development of the genetic test for Huntington Disease a disease that runs in her own family decided against having that very test. For her, living with the uncertainty about her own genetic status is better than knowing for sure. Because genes are shared within families, a genetic test of one person is also a test of a whole family. Some relatives want to know; others do not.

Research has shown that genetic information spreading through families, often without any proper explanation, can bring on discord and deep divisions fueled by anger and guilt. And then, there is also the sad history of the misuse of genetic information, particularly the debacle of eugenics policies practiced widely in the U.S. during the first half of the last century. An abundance of prejudice, coupled with baseless beliefs about inheritance, led to Americans being forcibly sterilized for supposedly having sub-par genes.

More than 60,000 people, typically poor and uneducated, were victims of these policies. Sadly, eugenic policies were vigorously pursued in this part of Virginia. There are real concerns that HR 1313 can usher in a new era of eugenics an era in which employers, under the guise of improving health, are able to use genetic information to weed out those who may develop health conditions that could interfere with their productivity at some point in the future.

Existing legislation, the Genetic Non-Discrimination Act of 2008 (or GINA), has restricted the use of genetic information in the workplace. These protections will evaporate if HR 1313 becomes law. Genetic testing needs to remain an individual decision a decision determined by ones own values, life experience, family realities and attitudes about privacy. People should decide on their own what, if any, genetic tests they want and follow up with their own doctors to determine a course of action once the results are received.

Wellness programs can continue to help their clients achieve better health through smoking cessation, better diets, more exercise, and the like without any need for requiring genetic testing. If such testing is inflicted on people, then genetic information may well become viewed as a mode of punishment something to be feared instead of the valuable adjunct to the personalized medical care that is the promise of genomic medicine.

See the article here:
Zallen: Genetic testing bill is modern eugenics - Roanoke Times