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
| Autor: | Chittaranjan S. Yajnik, Sreenivas Chavali, Smita R. Kulkarni, Rubina Tabassum, Om Prakash Dwivedi, Giriraj R. Chandak, Ganesh Chauhan, Seema Bhaskar, S. Prakash, M.V. Kranthi Kumar, Saurabh Ghosh, Nikhil Tandon, Dwaipayan Bharadwaj, Anubha Mahajan, Charles J. Spurgeon |
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| Rok vydání: | 2010 |
| Předmět: |
Male
endocrine system diseases Endocrinology Diabetes and Metabolism Genome-wide association study Type 2 diabetes 0302 clinical medicine Reference Values Ethnicity Cation Transport Proteins Aged 80 and over Genetics tRNA Methyltransferases 0303 health sciences SLC30A8 RNA-Binding Proteins Middle Aged 3. Good health Female TCF Transcription Factors Transcription Factor 7-Like 2 Protein medicine.medical_specialty Genotype India 030209 endocrinology & metabolism Single-nucleotide polymorphism Zinc Transporter 8 Biology White People 03 medical and health sciences Internal medicine Internal Medicine medicine Humans Potassium Channels Inwardly Rectifying CDKAL1 Cyclin-Dependent Kinase Inhibitor p16 Aged 030304 developmental biology Genetic association Homeodomain Proteins Genetic Variation nutritional and metabolic diseases Cyclin-Dependent Kinase 5 Odds ratio medicine.disease PPAR gamma Diabetes Mellitus Type 1 Endocrinology Diabetes Mellitus Type 2 biology.protein TCF7L2 Genome-Wide Association Study Transcription Factors |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db09-1386 |
| Popis: | OBJECTIVE Common variants in PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, 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 × 10−3 to 4.6 × 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 × 10−34). We also found significant association of PPARG and TCF7L2 with homeostasis model assessment of β-cell function (P = 6.9 × 10−8 and 3 × 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. |
| Databáze: | OpenAIRE |
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