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Changes in Gene May Make People Prone to Diabetes
posted 03/18/04

Researchers found four changes in the gene's code - called single nucleotide polymorphisms or "snips" - that were much more common in people with type 2 or adult-onset diabetes. The team looked at two groups - Finns and Ashkenazi Jews - often studied for genetic research because of their relative genetic purity.

Writing in the April issue of the journal Diabetes, the team said all four of the variations were found in a gene called 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. Diabetes is marked by a malfunction of these cells - in type 1 or juvenile diabetes, they are destroyed. But in type 2 diabetes, the body gradually loses its ability to respond properly to insulin. The researchers believe a person's genetics may predispose them to this condition, which can kick in with the help of outside factors such as overeating or a lack of exercise. Dr. Francis Collins, Director of the National Human Genome Research Institute, said "It may be a master regulator of cells that make insulin."

While there are no immediate implications, it may be possible one day to get a genetic screening and learn whether one is susceptible, said 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 genetics of 793 Finnish adults with typical type 2 diabetes and 413 people without diabetes. One of the four variants was found in 16 percent of the non-diabetics and in 22 percent of the diabetics, Collins said - raising the risk of diabetes by about 30 percent in those people. "We should quickly point out that this not the gene for diabetes. This is (just) a gene," Collins 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 "snips" 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 noted that,. "What we found was they are more common in the diabetic population. The difference might be 26 percent in cases and 20 percent in controls."

Collins said the task now is to examine other groups, but it was notable that two very different populations have the same four mutations. "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 In Control.com: Diabetes, April 2004.

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