March 3, 2014

Brett Smith for redOrbit.com Your Universe Online

A massive new study from a team of international researchers has identified mutations in a gene that can significantly reduce the risk of developing type 2 diabetes regardless of risk factors such as old age and being overweight. Seen in patients from multiple ethnic groups, the results showed a drug that imitates the influence of these mutations could be effectively used around the world.

In the study published in Nature Genetics the genetic evaluation of 150,000 patients showed that uncommon mutations in a gene called SLC30A8 scale back risk of type 2 diabetes by 65 percent. In previous research, the protein produced by SLC30A8 had been shown to play a critical role in the insulin secretion in the pancreas, and a typical variant in that gene was known to affect the risk of type 2 diabetes.

This work underscores that human genetics is not just a tool for understanding biology: it can also powerfully inform drug discovery by addressing one of the most challenging and important questions knowing which targets to go after, said study author David Altshuler, a Harvard Medical School professor at Massachusetts General Hospital.

To find mutations that reduce a persons probability of type 2 diabetes, the study team looked at participants with acute risk factors for diabetes, such as old age and obesity, who had not developed the disease and had healthy blood sugar levels. The team focused on a set of genes recognized earlier as playing a role in type 2 diabetes and looked for uncommon mutations.

They were able to find a genetic mutation that knocked out function of the SLC30A8 gene and that was highly prevalent in non-diabetic participants from Sweden and Finland. The protection against the disease was surprising, because scientific studies in mice had indicated that mutations in SLC30A8 might have the reverse effect increasing risk of type 2 diabetes. However, because this specified genetic variation was exceedingly uncommon outside of Finland, it proved difficult to obtain added evidence to corroborate the primary find.

These unpublished findings the result of a collaboration between American and Swedish scientists were shared with a group from deCODE genetics, a biopharmaceutical company based in Reykjavk, Iceland. The company researchers then found a subsequent mutation in an Icelandic population. The second mutation independently decreased risk for type 2 diabetes and decreased blood sugar in non-diabetics without apparent unfavorable effects.

Finally, the joint study team was able to identify ten more protective mutations in the same gene. With all the mutations considered together, one copy of a defective version of SLC30A8 was shown to have a 65 percent reduction in risk of diabetes.

This discovery underscores what can be accomplished when human genetics experts on both sides of the Atlantic come together to apply their craft to founder populations, enabling us to find rare mutations with large effects on disease risk, said Kari Stefannson, CEO of deCODE genetics.

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Genetic Mutation Found That Lowers Odds Of Developing Diabetes