Replication Study For The Association Of TCF7L2 Rs12255372 And Rs7903146 With Susceptibility To Type 2 Diabetes In A Chinese Han Population

Objective To explore whether the polymorphisms of rs12255372 and rs7903146 in transcription factor 7-like 2 (TCF7L2) were associated with type 2 diabetes mellitus (T2DM) in samples from Hunan Hengyang Chinese Han population.Methods 574 subjects, aged > 30 years from the population representative in the Second Affiliated Hospital of South China University, since August, 2008 to Septemper, 2009, were enrolled in the study. They were classified into three groups, according to the diagnostic criteria of WHO in 1999, 236 T2DM patients, 120 impaired glucose regulation (IGR) patients, and 218 normol glucose tolerance (NGT) subjects. All the genotypes of rs12255372 and rs7903146 polymorphisms in TCF7L2 were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP).Results1. The genotype frequencies of TCF7L2 rs12255372 GG, GT and TT were 93.6%, 6.4% and 0%, and rs7903146 CC, CT and TT were 91.5%, 8.5% and 0%, which both were in agreement with Hardy-Weinberg equilibrium(P>0.05).2. No differences were found in TCF7L2 rs12255372 GG/GT and rs12255372 G/T between the groups of T2DM, IGR, NGT(rs372GG/GT: X2=0.56, P=0.76, rs372G/T: X2=0.54, P=0.77), and the groups of T2DM+IGR, NGT(rs372GG/GT: X2=0.52, P=0.47, rs372G/T: X2=0.50, P=0.48). Also, no differences were found in TCF7L2 rs7903146 CC/CT and rs7903146 C/T between the groups of T2DM, IGR, NGT ( rs146CC/CT: X2=1.27, P=0.53, rs146C/T: X2=1.21, P=0.55), and the groups of T2DM+IGR, NGT( rs146CC/CT: X2=1.23, P=0.27, rs146C/T: X2=1.18, P=0.28). 3. No differences at the clinical datum and biochemical indicators were observed between TCF7L2 rs12255372 GG and GT, and rs7903146 CC and CT. Only the comparison of levels of low density lipoprotein cholesterol (LDL-C) between rs12255372 GG and GT, showed marginal association, with P=0.05.4. Single nucleotide polymorphisms (SNPs) rs12255372 and rs7903146 were in high linkage disequilibrium (LD) with D'=0.877, r2=0.588.5. The logistic regression analysis demonstrated that, no differences of the genotype and allelic frequencies at rs12255372 were found between the groups of T2DM, IGR and NGT, and the groups of T2DM+IGR, NGT, so did rs7903146.Conclusions We can't find association of TCF7L2 rs12255372 and rs7903146 with susceptibility to type 2 diabetes or impaired glucose regulation in a Hunan Hengyang Chinese Han population. Due to the low frequency of the risk allele, its attribution to the susceptibility to T2DM in Chinese population may be unimportant.