Common Variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE Genes Are Associated With Type 2 Diabetes and Impaired Fasting Glucose in a Chinese Han Population
Loos, Ruth J.F.
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CitationWu, Ying, Huaixing Li, Ruth J. F. Loos, Zhijie Yu, Xingwang Ye, Lihua Chen, An Pan, Frank B. Hu, and Xu Lin. 2008. Common Variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE Genes Are Associated With Type 2 Diabetes and Impaired Fasting Glucose in a Chinese Han Population. Diabetes 57(10): 2834-2842.
AbstractOBJECTIVE— Genome-wide association studies have identified common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, HHEX/IDE, EXT2, and LOC387761 loci that significantly increase the risk of type 2 diabetes. We aimed to replicate these observations in a population-based cohort of Chinese Hans and examine the associations of these variants with type 2 diabetes and diabetes-related phenotypes. RESEARCH DESIGN AND METHODS— We genotyped 17 single nucleotide polymorhisms (SNPs) in 3,210 unrelated Chinese Hans, including 424 participants with type 2 diabetes, 878 with impaired fasting glucose (IFG), and 1,908 with normal fasting glucose. RESULTS— We confirmed the associations between type 2 diabetes and variants near CDKAL1 (odds ratio 1.49 [95% CI 1.27–1.75]; P = 8.91 × 10−7) and CDKN2A/B (1.31 [1.12–1.54]; P = 1.0 × 10−3). We observed significant association of SNPs in IGF2BP2 (1.17 [1.03–1.32]; P = 0.014) and SLC30A8 (1.12 [1.01–1.25]; P = 0.033) with combined IFG/type 2 diabetes. The SNPs in CDKAL1, IGF2BP2, and SLC30A8 were also associated with impaired β-cell function estimated by homeostasis model assessment of β-cell function. When combined, each additional risk allele from CDKAL1-rs9465871, CDKN2A/B-rs10811661, IGF2BP2-rs4402960, and SLC30A8-rs13266634 increased the risk for type 2 diabetes by 1.24-fold (P = 2.85 × 10−7) or for combined IFG/type 2 diabetes by 1.21-fold (P = 6.31 × 10−11). None of the SNPs in EXT2 or LOC387761 exhibited significant association with type 2 diabetes or IFG. Significant association was observed between the HHEX/IDE SNPs and type 2 diabetes in individuals from Shanghai only (P < 0.013) but not in those from Beijing (P > 0.33). CONCLUSIONS— Our results indicate that in Chinese Hans, common variants in CDKAL1, CDKN2A/B, IGF2BP2, and SLC30A8 loci independently or additively contribute to type 2 diabetes risk, likely mediated through β-cell dysfunction.
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