Genetic Polymorphisms Associated With Predisposition To Type 2 Diabetes

WASHINGTON (Reuters) - Variants of a gene that helps control pancreatic and liver cells may make certain people prone to type 2 diabetes, U.S. and Finnish researchers said on Thursday.

Writing in the April issue of the journal Diabetes, published online March 11, the team said they had identified four single nucleotide polymorphisms (SNPs) in the gene for hepatocyte nuclear factor 4 alpha or HNF4A.

This gene acts as a master switch to regulate hundreds of other genes. In the beta cells of the pancreas, it helps control the secretion of insulin in response to glucose. “It may be a master regulator of cells that make insulin,” senior investigator Dr. Francis Collins, Director of the National Human Genome Research Institute, said in a telephone interview.

While there are no immediate implications, it may be possible one day that genetic screening could identify susceptibility to diabetes, said Dr. Collins, adding: “It would be nice to know when you are 21 so you could do something to prevent it.”

His team looked at the genotypes of 793 Finnish adults with typical type 2 diabetes and 413 people without diabetes.

One of the four SNPS was found in 16% of the non-diabetics and in 22% of the diabetics, Dr. Collins said -- raising the risk of diabetes by about 30% in those people.

“We should quickly point out that this not the gene for diabetes. This is (just) a gene,” he cautioned. “There will be probably dozens by the time the dust settles.”

Another team, led by Dr. Alan Permutt of the Washington University School of Medicine in St. Louis, studied 100 SNPs in 275 Ashkenazi Jewish adults in Israel with type 2 diabetes and 342 non-diabetics used as controls.

They homed in on the same four variations. “These markers are common in the general population,” Dr. Permutt said in a telephone interview. “What we found was they are more common in the diabetic population. The difference might be 26% in cases and 20% in controls.”

Dr. Collins said the task now is to examine other groups, but it was notable that two very different populations have the same four polymorphisms.

“This is probably a variant that’s been around a long time,” he said. “We’d love to know if this is one of these ‘thrifty genes’ that people have talked about - whether this might have helped you if you got into a tough situation with famine.”

The thrifty-gene hypothesis holds that obesity and diabetes are now so common because humans evolved in times when famine was the rule, and those with genes that help make use of every calorie survived better.

“Now with our situation that variant turns around and bites you,” Collins said.

Source: Diabetes 2004;53:1141-1149 [ Google search on this article ]

MeSH Headings:Polymorphism, Single NucleotideCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.