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Association Study of the Genetic Polymorphisms of the Transcription Factor7- like 2 (TCF7L2) Gene and Type 2 Diabetes in the Chinese Population

¹Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
²Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
³Graduate Institute of Clinical Medicine, National Taiwan University Medical College, Taipei, Taiwan
⁴Department of Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA, USA

Correspondence: leeming{at}ntu.edu.tw

Correspondence: leeming{at}ntu.edu.tw

Key Words: transcription factor 7-like 2 • TCF7L2 • type 2 diabetes • single nucleotide polymorphism • haplotype

Background: Genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene is one of the few validated genetic variants with large effects on the risk of type 2 diabetes in the populations of European ancestry.

Design and Methods: We genotyped 20 single nucleotide polymorphisms (SNPs) across the TCF7L2 gene in 1,520 unrelated subjects from a Han Chinese population in Taiwan. The associations of SNPs and haplotypes with type 2 diabetes and linkage disequilibrium (LD) structure of the TCF7L2 gene were analyzed.

Results: The previously reported SNPs rs7903146 T and rs12255372 T alleles of the TCF7L2 gene were rare and were not associated with type 2 diabetes in a Chinese population, which may attribute to the low frequencies of these two SNPs. SNP rs290487 located in a LD block close to the 3' end of the gene was associated with type 2 diabetes (allele-specific p=0.0021; permuted p= 0.03). The odds ratio was 1.36 for the CT genotype (95 percent confidence interval: 1.08 -1.71; p=0.0063) and 1.51 for the CC genotype (95 percent confidence interval: 1.10 -2.07; p= 0.0085) as compared to the TT genotype, corresponding to a population attributable risk fraction of 18.7 %. The haplotypes composed of rs290487 were also significantly associated with type 2 diabetes (global p= 0.012).

>Conclusion: We identified a novel risk-conferring genetic variant of TCF7L2 for type 2 diabetes in a Chinese population. Our data suggested that the TCF7L2 genetic polymorphisms are major determinants for risk of type 2 diabetes in the Chinese population.

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