The authors then performed a large meta-analysis of 36 studies examining the association of type 2 diabetes mellitus (T2DM) with polymorphisms in the TCF7L2 gene in various ethnicities, containing rs7903146 C-to-T (IVS3C>T), rs7901695 T-to-C (IVS3T>C), a rs12255372 G-to-T (IVS4G>T), and rs11196205 G-to-C (IVS4G>C) polymorphisms and to evaluate the size of gene effect and the possible genetic mode of action.
The meta-analysis results demonstrated that TCF7L2 rs4506565, rs7901695, rs11196205 and rs12255372 polymorphisms were all significantly associated with susceptibility to T2DM in general population.
Four single nucleotide polymorphisms (rs290487, rs7903146, rs11196205, and rs12255372), closely associated with type 2 diabetes in the Eastern Asia population, were genotyped and analyzed.
Adjusting also for T2D-related covariates, body mass index (BMI), and ancestry did not change the results substantively (rs7901695, p = 0.003; rs7903146, p = 0.005; rs11196205, p = 0.001; and rs12255372, p = 0.005).
The minor alleles of rs7903146, rs11196205, and rs12255372 showed significant associations with type 2 diabetes (OR=1.48, P=2.7 x 10(-4); OR=1.39, P=4.6 x 10(-4); OR=1.70, P=9.8 x 10(-5), respectively) in the combined sample sets.
We genotyped 309 German subjects at increased risk for type 2 diabetes for single nucleotide polymorphisms (SNPs) rs7903146, rs12255372, rs11196205, and rs7895340 in TCF7L2 and performed oral glucose tolerance tests before and after a 9-month lifestyle intervention.
We report replication of association of four of the six SNPs with T2DM in this Khatri Sikh sample [rs7903146, (p = 0.010); rs11196205, (p = 0.011); rs10885409, (p = 0.002) and rs4918789, (p = 0.029)], under a dominant model conferring odds ratios (ORs) of 1.39, 1.44, 1.57 and 1.36, respectively.
These results suggest that TCF7L2 variants rs7903146 rs12255372, and rs11196205 are significantly associated with angiographically diagnosed CAD, specifically in patients with T2DM.
We compared genotype frequencies in subjects with type 2 diabetes with those with NGT and found marginal association for rs7901695 (P = 0.05; odds ratio [OR] 1.51); comparison between NGT control subjects and the combined type 2 diabetes/IGT case group showed strong association with rs7901695 and rs7903146 (P = 0.008-0.01; OR 1.53-1.57) and marginal association with rs11196205 and rs12255372 (P = 0.07 and P = 0.04, respectively).