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Diabetes Publish Ahead of Print published online ahead of print May 9, 2008
DOI: 10.2337/db07-1583
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Original Research

Implication of Genetic Variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2 and FTO in Type 2 Diabetes and Obesity in 6719 Asians

Maggie C.Y. Ng1, Kyong Soo Park2, Bermseok Oh3, Claudia H.T. Tam1, Young Min Cho2, Hyoung Doo Shin4, Vincent K.L. Lam1, Ronald C.W. Ma1, Wing Yee So1, Yoon Shin Cho3, Hyung-Lae Kim3, Hong Kyu Lee2, Juliana C.N. Chan1,,5, and Nam H. Cho6

From the 1Department of Medicine and Therapeutics and
5Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
3Center for Genome Science, National Institute of Health, Seoul, Korea
4Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea
6Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Korea

Objective: Recent genome-wide association studies have identified six novel genes for type 2 diabetes (T2D) and obesity and confirmed TCF7L2 as the major T2D gene up to date in Europeans. However, the implications of these genes in Asians are unclear.

Research design and methods: We studied 13 associated single nucleotide polymorphisms (SNPs) from these genes in 3041 patients with T2D and 3678 controls of Asian ancestry from Hong Kong and Korea.

Results: We confirmed the associations of TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/CDKN2B, IGF2BP2 and FTO with risk for T2D, with odds ratios ranged from 1.13 to 1.35 (1.3x 10–12 < Punadjusted <0.016). In addition, the A allele of rs8050136 at FTO was associated with increased body mass index in the control subjects (Punadjusted=0.008). However, we did not observe significant association of any genetic variants with surrogate measures of insulin secretion or insulin sensitivity indices in a subset of 2662 control subjects. Compared to subjects carrying 0, 1 or 2 risk alleles, each additional risk allele was associated with 17% increased risk, and up to 3.3-fold increased risk for T2D in those carrying 8 or more risk alleles. Despite most of the effect sizes being similar between Asians and Europeans in the meta-analyses, the ethnic differences in risk allele frequencies in most of these genes lead to variable attributable risks in these two populations.

Conclusions: Our findings support the important but differential contribution of these genetic variants for T2D and obesity in Asians as compared to Europeans.

Correspondence: maggieng{at}cuhk.edu.hk

Key Words: Genome-wide association • type 2 diabetes • obesity • Asian


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