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Submitted on April 17, 2007
Accepted on June 26, 2007
Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
* To whom correspondence should be addressed. E-mail: maggieng{at}cuhk.edu.hk.
Objective: 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.
Design: We attempt to examine 22 tagging SNPs spanning across the TCF7L2 gene for association with T2D in Hong Kong Chinese. We firstly studied a case-control sample involving 433 hospital cases with familial early-onset type 2 diabetes and 419 normal controls, and further studied the associated SNPs in 450 members of 142 diabetic families.
Results: 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 (OR[95%CI] = 2.11[1.04-4.26]) while 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 contribute 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).
Conclusions: Our results are consistent with others' findings that variations at TCF7L2 contribute to type 2 diabetes, 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.
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C.-S. Ku, M. Khaw, and K. S. Chia Comment on: Chang et al. (2007) Association Study of the Genetic Polymorphisms of the Transcription Factor 7-like 2 (TCF7L2) Gene and Type 2 Diabetes in the Chinese Population: Diabetes 56:2631 2637 Diabetes, December 1, 2007; 56(12): e22 - e22. [Full Text] [PDF]
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