Three gene variants boost diabetes risk.

In a large study, researchers have linked small variations in three genes to type 2 diabetes. The information may prove useful in the development of a screening method to determine who is most likely to develop the disease.

Earlier, smaller studies had associated the three gene variants with type 2 diabetes. Valeriya Lyssenko of Lund University in Malmo, Sweden, and her colleagues set out to determine whether detecting common forms, or alleles, of nine diabetes-linked genes could predict who would develop the disease among a large population.

For their study, the researchers randomly selected 7,061 men and women who were participants in the Malmo Preventive Project, a massive, long-term clinical trial that began in the 1970s and followed each person for about 22 years. Lyssenko's team collected each person's medical history and studied analyses of their DNA. Almost 1,500 people in the sample developed type 2 diabetes.

Certain alleles of three genes--PPARG, TCF7L2, and KCNJ11--increased the risk of developing type 2 diabetes. People with all three risky variants were almost three times as likely to show the disease as were people who carried none of the alleles.

The researchers also calculated that these risk alleles strongly influence the numbers of cases. For example, if the variant of TCFTL2 were eliminated from the population, there'd be 22 percent fewer cases of type 2 diabetes. "These high numbers most likely reflect that these three alleles are common in the population," Lyssenko says.

Because the three alleles appear to be independently associated with increased risk of developing diabetes, each one probably has a unique role in the disease, Lyssenko adds.--K.T.