Replication and identification of novel variants at TCF7L2 associated with type 2 diabetes in Hong Kong Chinese.

Variations at a large linkage disequilibrium (LD) block of transcription factor 7-like 2 gene (TCF7L2) were reported to be associated with type 2 diabetes (T2D) in Icelandic, Danish and European-American populations and further replicated in other populations of European, African, and Asian ancestries. However, data for Chinese and comprehensive survey of the whole gene are lacking. We attempted to examine 22 tagging single-nucleotide polymorphisms (SNPs) spanning across the TCF7L2 gene for association with T2D in Hong Kong Chinese. We first studied a case-control sample involving 433 hospital cases with familial early-onset T2D and 419 normal controls and further studied the associated SNPs in 450 members of 142 diabetic families. Two of the previously reported risk alleles at rs11196205 (C) and rs7903146 (T) were rare in Chinese (0.013 and 0.024, respectively, in controls). Rs11196205 was associated with T2D [odds ratio (OR) [95% confidence interval (CI)] = 2.11 (1.04-4.26)], whereas the association for rs7903146 [OR (95% CI) = 1.27 (0.71-2.29)] was not significant in the case-control sample. Interestingly, another SNP (rs11196218 G allele) located in adjacent LD block conferred independent risk for T2D [OR (95%CI) =1.43 (1.14-1.79)] and contributed high-population attributable risk of 42%. The association finding of rs11196218 and its haplotype for T2D was also replicated in the family sample (P < 0.05). Our results are consistent with others' findings that variations at TCF7L2 contribute to T2D, including Chinese. The presence of association signals spanning several LD blocks warrants further examination of extended regions to reveal the causal variant(s) for this important T2D gene.