The rs7903146 was genotyped in 1) a population-based sample of 587 twins (55-64 yr) with glucose tolerance ranging from normal to type 2 diabetes and 2) a population of 196 nondiabetic young (22-31 yr) and elderly (57-66 yr) twins.
Three common variants (Lys23 of KCNJ11, Pro12 of PPARG, and the T allele at rs7903146 of TCF7L2) have been shown to be predisposed to type 2 diabetes mellitus across many large studies.
A case-control study was performed in Han Chinese subjects with normal control (n=152) and T2DM (n=227), we genotyped rs7903146 and rs11196218 at TCF7L2, rs13266634 at SLC30A8, rs3811951 at PCSK1 and rs2021785 at PCSK2.
The rs2476601C/T, rs689A/T, and rs7903146C/T polymorphisms were found to be associated with the risk of LADA, thereby indicating that, genetically, LADA could be an admixture of both T1D and T2D.
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.
Significant associations were found between type 2 diabetes and rs7903146, rs12255372, rs11196205, rs7901695, rs7895340 and rs4506565, with summary odds ratios (ORs) (95% confidence interval) of 1.39 (1.34-1.45), 1.33 (1.27-1.40), 1.20 (1.14-1.26), 1.32 (1.25-1.39), 1.21 (1.13-1.29) and 1.39 (1.29-1.49), respectively.
Together, data from our study show that TCF7L2-rs7903146 is associated with PDR in Caucasian T2DM and suggest that TCF7L2 promotes pathological retinal neovascularization via ER stress-dependent upregulation of VEGFA.
Our results point to a protein complex binding across rs7903146 within TCF7L2 and suggests a possible mechanism by which this locus confers its T2D risk.
The minor allele of each variant was significantly associated with type 2 diabetes; the greatest risk of developing the disease was conferred by rs7903146, with an allelic odds ratio (OR) of 1.31 (95% CI: 1.11 - 1.56, p = 1.96 x 10(-3)).
After adjusting for age, gender, drinking, smoking and body mass index (BMI), the association of <i>TCF7L2</i> rs7903146C>T and rs290481 T>C polymorphisms with T2DM was determined.
There are conflicting reports about the significance of TCF7L2 single nucleotide polymorphism rs7903146, a single nucleotide polymorphism found to be associated with type 2 diabetes mellitus in several genomewide association studies, and insulin sensitivity.
Adjusting also for T2D-related covariates, body mass index (BMI), and ancestry did not change the results substantively (rs7901695, p = 0.003; rs7903146</span>, p = 0.005; rs11196205, p = 0.001; and rs12255372, p = 0.005).
Thus, we aimed to investigate the contribution of rs1111875 (HHEX), rs1800961 (HNF4α), rs5219 (KCNJ11), rs1801282 (PPARγ), rs10811661 (CDKN2A/2B), rs13266634 (SLC30A8), rs12779790 (CDC123/CAMK1D), rs7903146 (TCF7L2), rs9282541 (ABCA1) and rs13342692 (SLC16A11) polymorphisms in the genetic background of Maya population to associate their susceptibility to develop T2D.
We investigate the association between gene variant rs7903146 and metabolic parameters and examine in vitro and ex vivo gene expression of <i>TCF7L2</i> in human adipose tissue and progenitor cells from two independent populations of young healthy men with increased risk of type 2 diabetes due to low birth weight (LBW).
Variants of SNPs rs7903146, rs1552224 and rs11642841 in the control group and rs7903146 in T2DM group showed significant association with both BMI and WC.
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.
In summary, our data show that the TCF7L2 rs7903146 polymorphism, a known risk factor for type 2 diabetes in the general population, also associates with NODAT.
Comparison between allele and genotype frequencies of these SNPs in patients and controls showed marginal association for rs7903146 and rs290487 with type 2 diabetes (p = 0.063, OR 1.982, 95% CI 1.128-3.485; p = 0.071, OR 1.237, 95% CI 0.983-1.557, respectively).
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.