A microsatellite, DG10S478, within intron 3 of the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4) was associated with type 2 diabetes (P = 2.1 x 10(-9)).
These results extend previous observations to other ethnic groups, and strongly confirm that TCF7L2 genotype is a major risk factor for development of T2D.
Recently, case-control studies demonstrated that a TCF7L2 (transcription factor 7-like 2 gene) noncoding variant (rs7903146 T at-risk allele) was strongly associated with an increased risk of type 2 diabetes.
These data provide replicating evidence that variants in TCF7L2 increase the risk for type 2 diabetes and novel evidence that the variants likely influence both insulin secretion and insulin sensitivity.
Three common variants (Lys23 of KCNJ11, Pro12 of PPARG, and the T allele at rs7903146 of TCF7L2) have been shown to predispose to type 2 diabetes mellitus across many large studies.
Recently, TCF7L2 variants, including the microsatellite marker DG10S478 and the nearly perfectly linked SNP rs12233372, were identified to associate with type 2 diabetes.
A microsatellite, DG10S478, within intron 3 of the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4) was associated with type 2 diabetes (P = 2.1 x 10(-9)).
The overall evidence for association for these variants (P = 4.4 x 10(-14) combining case-control and family-based analyses for rs4506565) exceeds genome-wide significance criteria and clearly establishes TCF7L2 as a type 2 diabetes susceptibility gene of substantial importance.
These data provide evidence that TCF7L2 is a major determinant of type 2 diabetes risk in European populations and suggests that this transcription factor plays a key role in glucose homeostasis.
We identify T2D-associated variants in an intergenic region of chromosome 11p12, contribute to the identification of T2D-associated variants near the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, and confirm that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T2D risk.
We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk.
It also provides evidence that variations in TCF7L2 may play a crucial role in the pathogenesis of type 2 diabetes by influencing both insulin secretion and insulin resistance.
The discovery of TCF7L2 as a diabetes gene illustrates that novel true diabetes genes can be found, their association with type 2 diabetes replicated and their effect incorporated into risk prediction models.
The gene encoding transcription factor 7-like 2 (TCF7L2) has been identified as a type 2 diabetes locus from genome-wide linkage studies and subsequent association analysis.
Nevertheless, 2006 heralded identification of the most important type 2 diabetes susceptibility gene known so far, TCF7L2, and in 2007 large-scale genome-wide association studies are destined to provide novel insights into the genetic architecture and biology of type 2 diabetes.