Iceland study finds important diabetes gene

A single genetic change could predispose close to 40 percent of the population to type-2 diabetes, researchers said on Sunday.

The gene, identified in a study of Iceland’s comprehensive genetic records, is carried by 38 percent of the Northern European populations studied, and is also common among African-Americans, the researchers said.

Writing in the journal Nature Genetics, Kari Stefansson of DeCode Genetics and colleagues said their finding could help in the development of an easy test for diabetes risk and might also lead to better drugs for the disease, which affects nearly 200 million people worldwide and 18 million people in the United States alone.

“If you have one copy of this variant, which 38 percent of people do, your risk of developing type-2 diabetes is increased by 40 percent,” Stefansson, who is chief executive officer of DeCode, said in a telephone interview.

“Seven percent have two copies and have a 140 percent increase in risk. If you would remove this variant out of the population, you would remove basically 20 percent of the type-2 diabetes cases from our society.”

Type-2 diabetes was once known as adult-onset diabetes, and differs from type-1, or juvenile, diabetes. With an inability to use and produce insulin properly, sufferers end up with too much glucose in their blood and have high rates of heart disease, blindness, nerve damage and limb loss.

Type-2 diabetes is associated with obesity, overweight and a lack of exercise and is being found in children more commonly worldwide.

“It is a disease that occurs at the interface of genes and environment,” Stefansson said.

The variant his team found, called TCF7L2, is associated with a younger onset of the condition, and sufferers appear to be thinner than the average type-2 diabetes patient.

BIOLOGICAL CAUSES

“This discovery sheds new light on the biological causes of the disease. Importantly, virtually all of this risk can be captured by looking at a single-letter change in DNA - ideal for the development of a genetic test for assessing individual risk and developing more personalized and effective prevention strategies,” Stefansson said.

“This is also an exciting starting point for the discovery of new drugs, and we are actively pursuing the development of both diagnostic and therapeutic products to better prevent and treat type-2 diabetes,” he added.

While his team studied mostly northern Europeans - Icelanders, Danes and U.S. citizens - Stefansson said he also saw other variants that are found in people around the world that also confer diabetes risk.

Iceland-based DeCode specializes in trolling the country’s DNA database for information. Virtually the entire population of Iceland, a highly inbred group, has voluntarily donated DNA to be sequenced, analyzed and published.

The DeCode team found the gene first in Icelanders with diabetes, and then looked in 228 Danish women with type-2 diabetes and 539 who did not have the condition.

They also looked at 361 American diabetics of European descent and 530 similar people without diabetes.

They said the TCF7L2 gene can be found on chromosome 10q. It is a transcription factor, a gene that controls another gene, in this case the well-known Wnt signaling pathway. Wnt is involved in key developmental and growth regulatory mechanisms of cells.

Provided by ArmMed Media
Revision date: July 9, 2011
Last revised: by Andrew G. Epstein, M.D.