Common Variants Of The TCF7L2 Gene With Type 2 Diabetes And Impaired Glucose Regulation In A Chinese Han Population

Objective To determine whether common variants of TCF7L2 gene is associated with type 2 diabetes and impaired glucose regulation in Anhui Chinese population.Methods In this case-control study, we chose patients with type 2 diabetes (300 cases), and impaired glucose regulation (300 cases), and normal control subjects (300 cases)(all from the First Affiliated Hospital of Anhui Medical University), and collected clinical characteristics and blood, extracted DNA. PCR amplified fluorescence-labeled target gene, which then hybridized with probes on the surface of biochip, and got the scanning results. All the data was analyzed by one-way ANOVA and K-W tests, finally determine whether variant of six SNPs of TCF7L2 gene related to type 2 diabetes and impaired glucose regulation. And by measuring GLP-1, HOMA-IR, HOMA-β, we also analyze whether those SNPs associated with GLP-1, HOMA-IR, HOMA-β.Results Four of the six SNPs: rs11196218, rs12775879, rs290487, rs290481 are associated with T2DM, IGR, and NGT group. In our set of 900 Chinese individuals, the frequencies of risk alleles of four SNPs (rs11196218, rs12775879, rs290487, rs290481) were higher in the T2DM and IGR group than in the NGT group(P<0.05) and significant differences were found for allelic frequencies: 0.41 in T2DM, 0.39 in IGR vs. 0.26 in NGT for rs11196218; 0.38 in T2DM, 0.31 in IGR vs. 0.24 in NGT for rs12775879; 0.43 in T2DM, 0.38 in IGR vs. 0.29 in NGT for rs290487; 0.58 in T2DM, 0.39 in IGR vs. 0.33 in NGT for rs290481. The rate of T2DM increased with an increasing dose of allele T of rs290487 (OR = 1.43, 95%CI= 1.23–1.67, P<0.001); the rate of IGR increased with an increasing dose of allele T of rs12775879 (OR = 1.37, 95%CI= 1.09–1.71, P=0.008). According to the biochip results, we divided all the subjects into three groups; we did not observe any significant association between the risk alleles and WHR, SBP, DBP, TG, TCHO. Compared with wild genotype, heterozygote and homozygote genotype have higher levels of FPG, P2hG and HOMA-β, but lower levels of HOMA-IR (P<0.05). However, both carriers of rs290487, there's no differences for GLP-1(0min) and GLP-1(30min) between T2DM and NGT group (P>0.05); both carriers of rs12775872, there's no differences for GLP-1(0min) and GLP-1(30min) between IGR and NGT group (P>0.05). Conclusions Collectively, our data show that common variants of TCF7L2 gene are associated with T2DM and IGR in Chinese population. Also, variants in TCF7L2 gene are associated with HOMA-IR and HOMA-β, which might be consistent with a state of relative incretin resistance. But GLP-1 secretion were not influenced by the TCF7L2 polymorphisms, which indicated us that further study should focus on the many chemical reactions GLP-1 participated in, and which is the most important ones to T2DM and insulin resistance.