The meta-analysis results demonstrated that TCF7L2 rs4506565, rs7901695, rs11196205 and rs12255372 polymorphisms were all significantly associated with susceptibility to T2DM in general population.
Our results revealed a strong association between risk T alleles in variants rs12255372 (OR: G/T=1.4233; T/T=2.0395) and rs4506565 (OR: A/T=1.6066; T/T=3.1301) and T2DM among the Saudi population of the Eastern Province of Saudi Arabia.
Given the overlap between PCOS and T2DM, we investigated the association of transcription factor-7-like 2 (TCF7L2) variants rs4506565, rs7903146, rs12243326, and rs12255372 with the susceptibility to PCOS.
The four tested TCF7L2 variants were in linkage disequilibrium, and 4-locus (rs4506565, rs7903146, rs12243326, rs12255372) haplotype analysis demonstrated that haplotype 1111 was negatively associated (Pc<0.001), while haplotypes 2222 (Pc=0.008) and 2211 (Pc=0.020) were positively associated with T2DM risk, after controlling for a number of covariates.
Significant associations were found between the six polymorphisms (rs7903146, rs12255372, rs11196205, rs7901695, rs7895340 and rs4506565) in the TCF7L2 gene andtype 2 diabetes</span> risk, and the other two polymorphisms (rs11196218 and rs290487) were not found to be significantly associated with type 2 diabetes.
Genome-wide association and meta-analysis in populations from Starr County, Texas, and Mexico City identify type 2 diabetes susceptibility loci and enrichment for expression quantitative trait loci in top signals.
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.