Exon sequencing and association analysis of polymorphisms in TCF7L2 with type 2 diabetes in a Chinese population

Aims/hypothesis Recently, variants in the transcription factor 7-like 2 (TCF7L2) gene have been found to be consistently associated with type 2 diabetes in different populations. In this study, we hypothesized that TCF7L2 also contributed to genetic susceptibility for type 2 diabetes in a Chinese population. MethodsWe looked for new variants by direct sequencing of all exons and intron-exon junctions of TCF7L2 in 100 Chinese type 2 diabetic patients, and then we genotyped five single nucleotide polymorphisms (SNPs) by Snapshot technology in 1,000 Chinese individuals. Results By sequencing, we identified six SNPs (c.1,637C > A; c.1,674C > G; c.1,709G > A; c.1,846C > G; c.1,888C > T; and c.1,876T > G), and three of them led to non-synonymous polymorphisms ( c.1,637C > A, His -> Gln or Pro -> Thr; c.1,674C > G, Pro. Arg; and c.1,709G > A, Ala -> Thr). All of them are rare except c.1,637C > A, which had a frequency of 0.23 for the minor A allele in 98 sequenced individuals. In a case-control study, one of the newly discovered SNPs (c.1,637C > A), together with four reported ones (rs7903146, rs12255372, rs290487 and rs3814573) were genotyped. Comparison between allele and genotype frequencies of these SNPs in patients and controls showed marginal (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). No association was found for rs12255372, rs3814573, c.1,637C > A and type 2 diabetes (p=0.278-1.000). Conclusions/interpretation With the current sample size, we did not find any mutation in the coding sequence of TCF7L2 that confers a genetic risk for type 2 diabetes in a Chinese population, and did not replicate some of the major positive results obtained in other populations.