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- Title
Implication of Genetic Variants Near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in Type 2 Diabetes and Obesity in 6,719 Asians.
- Authors
Ng, Maggie C. Y.; Park, Kyong Soo; Oh, Bermseok; Tam, Claudia H. T.; Young Min Cho; Hyoung Doo Shin; Lam, Vincent K. L.; Ma, Ronald C. W.; Wing Yee So; Yoon Shin Cho; Hyung-Lae Kim; Hong Kyu Lee; Chan, Juliana C. N.; Cho, Nam H.
- Abstract
OBJECTIVE--Recent genome-wide association studies have identified six novel genes for type 2 diabetes and obesity and continued TCF7L2 as the major type 2 diabetes gene 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 from these genes in 3,041 patients with type 2 diabetes and 3,678 control subjects of Asian ancestry from Hong Kong and Korea. RESULTS--We continued the associations of TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/CDKN2B, IGF2BP2, and FTO with risk for type 2 diabetes, with odds ratios ranging from 1.13 to 1.35 (1.3 x 10[sup -12] < P[sub unadjusted] < 0.016). In addition, the A allele of rs8050136 at FTO was associated with increased BMI in the control subjects (P[sub unadjusted] = 0.008). However, we did not observe significant association of any genetic variants with surrogate measures of insulin secretion or insulin sensitivity indexes in a subset of 2,662 control subjects. Compared with subjects carrying zero, one, or two risk alleles, each additional risk allele was associated with 17% increased risk, and there was an up to 3.3-fold increased risk for type 2 diabetes in those carrying eight 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 to type 2 diabetes and obesity in Asians compared with Europeans. Diabetes 57: 2226-2233, 2008
- Subjects
HUMAN genetic variation; TYPE 2 diabetes; OBESITY; GENETIC polymorphisms; ASIANS
- Publication
Diabetes, 2008, Vol 57, Issue 8, p2226
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db07-1583