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Diabetes 56:e23 2007
DOI: 10.2337/db07-1302
© 2007 by the American Diabetes Association
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Letter to the Editor

Response to 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

Yi-Cheng Chang1, Ken C. Chiu2, and Lee-Ming Chuang3

1 Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
2 Department of Diabetes, Endocrinology, and Metabolism, City of Hope National, Medical Center, Duarte, California
3 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Address correspondence and reprint requests to Lee-Ming Chuang, MD, PhD, Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Rd., Taipei, Taiwan. E-mail: leeming{at}ntu.edu.tw

We appreciate the comments from Ku et al. (1). Although previously genome-wide linkage studies were and, currently, genome-wide association studies are the preferred approaches for the search of genetic causes of complex diseases, such as type 2 diabetes, the candidate gene approach remains a very useful tool as a supplement to the whole-genome search. In some published genome-wide association studies of type 2 diabetes, this locus would fall off the screen when a stringent criterion for the positive association was applied (2). When we noticed that the frequencies of rs7903146 (intron 3) and rs12255372 (intron 4), previously reported to be associated with type 2 diabetes, were rare in the Chinese population, we extended our single nucleotide polymorphism (SNP) study to cover the whole gene (3). We then identified a novel SNP (rs290487 in intron 7) associated with type 2 diabetes, implying a population-attributable risk fraction of 18.7% in the Chinese population residing in Taiwan. Our study clearly demonstrated the role of the candidate gene approach in type 2 diabetes.

Furthermore, the association with the same SNPs or haplotype in different populations indicated a founder effect. Identification of a novel SNP association in the Chinese population residing in Taiwan suggested a different founder from that in the previously reported populations. Interestingly, Ng et al. (4) reported the association of rs11196218 (intron 4) with type 2 diabetes in a Chinese (mainly Cantonese) population residing in Hong Kong. Two different SNPs are associated with type 2 diabetes in two different Chinese populations, suggesting different ancestral origins of these two Chinese populations.

Received for publication September 12, 2007 and accepted in revised form September 12, 2007

REFERENCES

  1. Ku C-S, Khaw M, Chia KS: 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 56:e22, 2007. DOI: 10.2337/db07-1213[Free Full Text]
  2. Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, Timpson NJ, Perry JR, Rayner NW, Freathy RM, Barrett JC, Shields B, Morris AP, Ellard S, Groves CJ, Harries LW, Marchini JL, Owen KR, Knight B, Cardon LR, Walker M, Hitman GA, Morris AD, Doney AS; Wellcome Trust Case Control Consortium, McCarthy MI, Hattersley AT: Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316:1336–1341, 2007[Abstract/Free Full Text]
  3. Chang Y-C, Chang T-J, Jiang Y-D, Kuo S-S, Lee K-C, Chiu KC, Chuang L-M: 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
  4. Ng MC, Tam CH, Lam VK, So WY, Ma RC, Chan JC: Replication and identification of novel variants at TCF7L2 associated with type 2 diabetes in Hong Kong Chinese. J Clin Endocrinol Metab 92:3733–3737, 2007[Abstract/Free Full Text]

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This Article
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