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

被引：194

作者：

Wu, Ying ^{[1
,2
]}

Li, Huaixing ^{[1
,2
]}

Loos, Ruth J. F. ^{[3
]}

Yu, Zhijie ^{[1
,2
]}

Ye, Xingwang ^{[1
,2
]}

Chen, Lihua ^{[1
,2
]}

Pan, An ^{[1
,2
]}

Hu, Frank B. ^{[4
]}

Lin, Xu ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai, Peoples R China

[2] Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China

[3] Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England

[4] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

来源：

DIABETES | 2008年 / 57卷 / 10期

基金：

英国医学研究理事会; 中国国家自然科学基金;

关键词：

D O I：

10.2337/db08-0047

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

OBJECTIVE-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 x 10(-7)) and CDKN2A/B (1.31 [1.12-1.54]; P = 1.0 x 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 beta-cell function estimated by homeostasis model assessment of beta-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 x 10(-7)) or for combined IFG/type 2 diabetes by 1.21-fold (P = 6.31 x 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 beta-cell dysfunction.

引用

页码：2834 / 2842

页数：9

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