Impact of Common Variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the Risk of Type 2 Diabetes in 5,164 Indians

被引：150

作者：

Chauhan, Ganesh ^{[1
]}

Spurgeon, Charles J. ^{[2
]}

Tabassum, Rubina ^{[1
]}

Bhaskar, Seema ^{[2
]}

Kulkarni, Smita R. ^{[3
]}

Mahajan, Anubha ^{[1
]}

Chavali, Sreenivas ^{[1
]}

Kumar, M. V. Kranthi ^{[2
]}

Prakash, Swami ^{[2
]}

Dwivedi, Om Prakash ^{[1
]}

Ghosh, Saurabh ^{[4
]}

Yajnik, Chittaranjan S. ^{[3
]}

Tandon, Nikhil ^{[5
]}

Bharadwaj, Dwaipayan ^{[1
]}

Chandak, Giriraj R. ^{[2
]}

机构：

[1] CSIR, Inst Genom & Integrat Biol, Funct Genom Unit, Delhi, India

[2] CSIR, Ctr Cellular & Mol Biol, Genome Res Grp, Hyderabad, Andhra Pradesh, India

[3] King Edward Mem Hosp & Res Ctr, Diabet Unit, Pune, Maharashtra, India

[4] Indian Stat Inst, Human Genet Unit, Kolkata, India

[5] All India Inst Med Sci, Dept Endocrinol, New Delhi, India

来源：

DIABETES | 2010年 / 59卷 / 08期

关键词：

GENOME-WIDE ASSOCIATION; PRO12ALA POLYMORPHISM; INSULIN-SECRETION; GENETIC-VARIANTS; OBESITY; SUSCEPTIBILITY; RESISTANCE; GLUCOSE; LOCI; FTO;

D O I：

10.2337/db09-1386

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

OBJECTIVE-Common variants in PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, 1GF2BP2, and CDKAL1 genes have been shown to be associated with type 2 diabetes in European populations by genome-wide association studies. We have studied the association of common variants in these eight genes with type 2 diabetes and related traits in Indians by combining the data from two independent case-control studies RESEARCH DESIGN AND METHODS-We genotyped eight single nucleotide polymorphisms (PPARG-rs1801282, KCNJ11-rs5219, TCF7L2-rs7903146, SLC30A8-rs13266634, HHEX-rs1111875, CDKN2A-rs10811661, IGF2BP2-rs4402960, and CDKAL1-rs10946398) in 5,164 unrelated Indians of Indo-European ethnicity, including 2,486 type 2 diabetic patients and 2,678 ethnically matched control subjects. RESULTS-We confirmed the association of all eight loci with type 2 diabetes with odds ratio (OR) ranging from 1.18 to 1 89 (P = 1 6 x 10(-3) to 4.6 x 10(-34)). The strongest association with the highest effect size was observed for TCF7L2 (OR 1.89 [95% CI 1.71-2.09], P = 4.6 x 10(-34)). We also found significant association of PPARG and TCF7L2 with homeostasis model assessment of beta-cell function (P = 6.9 x 10(-3) and 3 x 10(-4), respectively), which looked consistent with recessive and under-dominant models, respectively CONCLUSIONS-Our study replicates the association of well-established common variants with type 2 diabetes in Indians and shows larger effect size for most of them than those reported in Europeans. Diabetes 59:2068-2074, 2010

引用

页码：2068 / 2074

页数：7

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