The meta-analysis results demonstrated that TCF7L2 rs4506565, rs7901695, rs11196205 and rs12255372 polymorphisms were all significantly associated with susceptibility to T2DM in general population.
Puerto Ricans with the TCF7L2-rs7903146 and rs12255372T2D risk genotypes, although still high, had better anthropometric profiles when adhering to a MedDiet, suggesting that this diet may offset unfavorable genetic predisposition.
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).
BMI and rs12255372 are associated with the risk of conversion to IGT and T2DM [OR = 1.07 (95% IC 1.0-1.14, p = .041; OR =2.14, 95% IC 1.01-4.55, p = .04 respectively), while the lactation shows a strong protective effects OR = 0.15 (95% IC 0.062-0.39, p = .00007), and an apparent interaction with rs12255372T decreasing the risk in carriers (OR =2.15; 95% IC 0.97-4.7, p = .05).
The <i>KCNJ11</i> SNP rs5210 was associated with T2DM, the <i>TCF7L2</i> SNP rs11196175 was associated with BMI and cholesterol and LDL levels, the <i>TCF7L2</i> SNP rs12255372 was associated with BMI and HDL, VLDL and triglyceride levels, and the <i>HNF4A</i> SNP rs1885088 was associated with LDL levels (P<0.05).
An interaction (p = 0.048) between TCF7L2 variants and coffee intake was apparent, with an inverse association between coffee and type 2 diabetes present among carriers of the diabetes risk allele (T) in rs12255372 (GG: HR 0.99 [95% CI 0.97, 1.02] per cup of coffee; GT: HR 0.96 [95% CI 0.93, 0.98]); and TT: HR 0.93 [95% CI 0.88, 0.98]).
The T-allele of the SNP rs12255372 of TCF7L2 (OR = 2.70, 95% CI = 1.12-6.49, P = 0.027) and the A-allele of PDX-1 D76N (OR = 3.93, 95% CI = 1.60-7.68, P = 0.002) were significantly associated with an increased risk of T2DM.
These findings suggest that the TCF7L2 rs12255372 (G>T) polymorphism might be one of the most important genetic factors associated with T2DM susceptibility, and that individuals in the Chinese Hui population who carry a G allele at this locus might be at risk to develop T2DM.
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.
For total participants and male, the distribution of rs12255372 alleles and the dominant model (Guanine Guanine (GG) genotype vs. Guanine Thymine (GT) genotype + Thymine Thymine (TT) genotype) showed significant difference between T2DM and control subjects (for allele: p = 0.013 and p = 0.002, respectively; for dominant model: p = 0.028 and p = 0.008, respectively).
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.
There was no evidence that rs12255372G/T and rs290487T/C polymorphisms increased T2DM risk (T vs. G, OR = 1.77, 95% CI = 0.88-3.56; C vs. T, OR = 1.08, 95% CI = 0.93-1.25).
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.
Individuals homozygous for rs7903146 and rs12255372</span> T2D risk alleles (TT/TT) expressed 2.6-fold greater levels of TCF7L2 mRNA compared to individuals homozygous for the non-risk alleles (CC/GG, p = 0.006), although differentially spliced TCF7L2 transcripts did not differ by T2D risk-associated genotype.
Four single nucleotide polymorphisms (rs290487, rs7903146, rs11196205, and rs12255372), closely associated with type 2 diabetes in the Eastern Asia population, were genotyped and analyzed.
In summary, by pooling all available qualified data from genetic studies on rs12255372 and T2DM, we have confirmed that rs12255372 is significantly associated with susceptibility to T2DM in the global population.
Three TCF7L2 polymorphisms (rs7903146, rs7901695 and rs12255372) have been analyzed by allelic discrimination assays in a cohort of 154 Italian patients with T2DM and 171 healthy controls.