Common coding variant in the TCF7L2 gene and study of the association with type 2 diabetes in Japanese subjects

AbstractGenetic variants of the transcription factor 7-like 2 (TCF7L2) gene affect the risk of type 2 diabetes in populations with multiple ethnic groups. However, a comprehensive survey of this gene has not been done for a Japanese population. Thus, we conducted this gene-based association study, in which the common genetic variants were analyzed. Using 24 Japanese type 2 diabetic subjects, we first screened a 9.5  kb region, which included the entire coding sequence, to assess potential functional variants of TCF7L2. Sequencing revealed a common coding variant (Pro477Thr) in exon 14 of TCF7L2 that was not enrolled in the public SNP database. Nineteen SNPs and the microsatellite DG10S478 were genotyped acros s the gene in 2,877 unrelated Japanese subjects. This independent screen identified the previously reported rs7903146 with a strongest association (alleleP = 0.0001, odds ratio = 1.59 [95% confidence interval 1.25–2.01]), but there was no significant association between Pro477Thr and type 2 diabetes (alleleP = 0.64). Expression of the Pro477Thr variant did not alter TCF7L2 expression in 30 lymphoblast cells. Although a genotypic effect of Pro477Thr on expression of TCF7L2 was not apparent, Pro477Thr was identified as a common variant of TCF7L2 in 2,877 Japanese subjects. Further functional studies ar e required to determine the possible effect of this coding variant on type 2 diabetes.
Source: Journal of Human Genetics - Category: Genetics & Stem Cells Source Type: research