Genetic Risk Factor Found for Diabetes

The variant is located in a gene encoding a protein called transcription factor 7-like 2 (TCF7L2).

The researchers, from deCODE Genetics (Reykjavik, Iceland), isolated the gene by following up on the results of a genome-wide linkage scan in Iceland that identified a promising region on chromosome 10. They genotyped 228 microsatellite markers--polymorphic signposts along the genome--in this region in more than 2,000 patients and controls. An analysis of the frequency of different alleles of these markers pinpointed a version of one marker with the gene encoding TCF7L2 that is about 1.5 times more common in patients than in controls. This represents a 50% increase in risk of T2D per copy carried (two copies of each chromosome are in every cell).

The research was repeated in Danish and U.S. subjects, where the at-risk version of the marker was found to confer an increased risk of 41% and 85%, respectively, per copy carried. For all of the cohorts combined, the at-risk allele confers an increased risk of about 45% for those carrying one copy and a 141% increase for those carrying two copies. By utilizing data from the HapMap project, the researchers were able to find a single nucleotide polymorphism (SNP) that correlates almost perfectly with the at-risk microsatellite. The results of the research were published in the January 15, 2006, online edition of Nature Genetics.

"This is a milestone in human genetics,” said senior author Kari Stefansson, CEO of deCode. "A common gene variant conferring elevated risk of T2D has been earnestly sought by the genetics community for many years. 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.”




Related Links:
deCODE Genetics