rs11196205

This case-control study examined 200 T2DM patients and 200 healthy controls from North India to assess association of TCF7L2 gene polymorphisms with type 2 diabetes risk. The TT genotype of rs4506565 was significantly more frequent in diabetic patients (49%) vs controls (32.5%, OR=1.99, p=0.0008), and the CC genotype of rs11196205 was more frequent in patients (51%) vs controls (30%, OR=0.41, p=0.001). The haplotype T-C was also significantly associated with T2DM (p=0.000384).

This case-control study investigated 25 T2DM-associated SNPs in a multi-ethnic Hawaiian cohort (291 GDM cases, 734 controls) and found ethnicity-specific associations with gestational diabetes. Key findings in Filipinos included rs1113132 (EXT2, OR=1.52, p=0.028), rs1111875 (HHEX, OR=1.5, p=0.047), rs2237892 (KCNQ1, OR=0.49, p<0.001), rs10830963 (MTNR1B, OR=0.63, p=0.025), and rs13266634 (SLC30A8, OR=0.58, p=0.011). In Japanese women, rs4402960 (IGFBP2, OR=0.5, p=0.031) and rs2237892 (KCNQ1, OR=0.5, p=0.03) were significant. Pacific Islanders showed associations with rs10830963 (MTNR1B, OR=0.52, p=0.037) and rs13266634 (SLC30A8, OR=2.43, p=0.03). No SNPs showed consistent associations across all three ethnic groups.

This prospective family-based cohort study examined TCF7L2 genetic variants in 1,094 Han Chinese subjects and found pleiotropic effects on diabetes progression. Variants in the exon 4 LD block (rs7903146, rs7079711, rs4506565, rs7895340) were associated with impaired insulin secretion and increased diabetes risk (hazard ratio = 2.61, p = 0.009), while 3' end variants (rs290481, rs290487) were associated with insulin resistance markers but not diabetes progression. TCF7L2 expression was inversely correlated with insulin resistance in human adipose tissue.

This study examined whether TCF7L2 SNPs (rs7903146, rs12255372, rs7901695, rs11196205, rs7895340) are associated with cardiovascular disease (CVD) and mortality in the ARIC cohort of 13,369 participants. The T-allele of rs7903146 was not significantly associated with incident coronary heart disease, ischemic stroke, CVD, or all-cause mortality in the full cohort or when stratified by race. A weak association with incident CHD was observed in whites with prevalent diabetes (HR = 1.21, p = 0.04) but not in blacks, suggesting TCF7L2's increased health risk is specific to diabetes rather than general cardiovascular disease.

iLOCi is a novel SNP interaction prioritization algorithm designed to detect gene-gene interactions (epistasis) in genome-wide association studies by accounting for marker dependencies separately in case and control groups. Validated on WTCCC data across seven complex diseases (bipolar disorder, coronary artery disease, Crohn's disease, hypertension, rheumatoid arthritis, type 1 diabetes, and type 2 diabetes), the algorithm identified disease-associated SNP pairs including hub SNPs such as rs1553460 for bipolar disorder and rs3785579 for coronary artery disease and rheumatoid arthritis, revealing both previously known disease genes (TCF7L2 for T2D, HLADQB1 for T1D) and novel disease-associated genes (CACNG1 for rheumatoid arthritis).

This replication study examined the association of TCF7L2 polymorphisms with type 2 diabetes in a Japanese population of 1,630 patients and 1,064 controls. All four tested SNPs (rs12255372, rs7903146, rs7901695, rs11196205) were significantly associated with type 2 diabetes, with rs12255372 showing the strongest association (OR=1.70, 95% CI=1.20-2.41, p=0.0024). The risk allele frequencies were substantially lower in the Japanese population compared to white populations, suggesting ethnic differences in genetic susceptibility to type 2 diabetes.

This association study of 1,110 non-diabetic participants examined TCF7L2 gene polymorphisms (rs7903146, rs12255372, rs7901695) and found that risk allele carriers have specifically impaired GLP-1-induced insulin secretion (p<0.02 for rs7903146 and rs12255372), consistent with a defect in the GLP-1 signaling pathway in pancreatic beta cells rather than reduced GLP-1 secretion. This functional deficit provides a mechanistic explanation for the increased type 2 diabetes risk conferred by these variants.

This study investigated whether TCF7L2 gene variants associated with type 2 diabetes in European populations also confer risk in Japanese populations. The SNP rs7903146 showed significant association with type 2 diabetes in combined Japanese samples (n=1,997; OR=1.69, 95% CI 1.21–2.36, p=0.002), demonstrating that TCF7L2 is a common type 2 diabetes susceptibility gene across ethnic groups.