Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs

Aims/hypothesis Evaluation of the association of 31 common single nucleotide polymorphisms (SNPs) with fasting glucose, fasting insulin, HOMA-beta cell function (HOMA-β), HOMA-insulin resistance (HOMA-IR) and type 2 diabetes in the Indian population. Methods We genotyped 3,089 sib pairs recruited in...

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Published in:	Diabetologia Vol. 55; no. 2; pp. 349 - 357
Main Authors:	Gupta, V., Vinay, D. G., Rafiq, S., Kranthikumar, M. V., Janipalli, C. S., Giambartolomei, C., Evans, D. M., Mani, K. R., Sandeep, M. N., Taylor, A. E., Kinra, S., Sullivan, R. M., Bowen, L., Timpson, N. J., Smith, G. D., Dudbridge, F., Prabhakaran, D., Ben-Shlomo, Y., Reddy, K. S., Ebrahim, S., Chandak, G. R.
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer-Verlag 01-02-2012 Springer Springer Nature B.V
Subjects:	Adult Alleles Biological and medical sciences Blood Glucose - metabolism Chronic illnesses Diabetes Diabetes Mellitus, Type 2 - ethnology Diabetes Mellitus, Type 2 - genetics Diabetes. Impaired glucose tolerance Endocrine pancreas. Apud cells (diseases) Endocrinopathies Epidemiology Etiopathogenesis. Screening. Investigations. Target tissue resistance Europe Family Health Female Genomes Genomics Genotype Glucose Human Physiology Humans India Insulin - blood Insulin - metabolism Insulin resistance Internal Medicine Male Medical sciences Medicine Medicine & Public Health Metabolic Diseases Middle Aged Migration Phenotype Polymorphism, Genetic Quantitative Trait Loci Risk Siblings Transients and Migrants Asia India Europe United Kingdom > UK Intermediate traits Type 2 diabetes Association Polymorphisms India Endocrinopathy Metabolic diseases Indian Polymorphism
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Summary:	Aims/hypothesis Evaluation of the association of 31 common single nucleotide polymorphisms (SNPs) with fasting glucose, fasting insulin, HOMA-beta cell function (HOMA-β), HOMA-insulin resistance (HOMA-IR) and type 2 diabetes in the Indian population. Methods We genotyped 3,089 sib pairs recruited in the Indian Migration Study from four cities in India (Lucknow, Nagpur, Hyderabad and Bangalore) for 31 SNPs in 24 genes previously associated with type 2 diabetes in European populations. We conducted within-sib-pair analysis for type 2 diabetes and its related quantitative traits. Results The risk-allele frequencies of all the SNPs were comparable with those reported in western populations. We demonstrated significant associations of CXCR4 (rs932206), CDKAL1 (rs7756992) and TCF7L2 (rs7903146, rs12255372) with fasting glucose, with β values of 0.007 ( p = 0.05), 0.01 ( p = 0.01), 0.007 ( p = 0.05), 0.01 ( p = 0.003) and 0.08 ( p = 0.01), respectively. Variants in NOTCH2 (rs10923931), TCF-2 (also known as HNF1B ) (rs757210), ADAM30 (rs2641348) and CDKN2A/B (rs10811661) significantly predicted fasting insulin, with β values of −0.06 ( p = 0.04), 0.05 ( p = 0.05), −0.08 ( p = 0.01) and −0.08 ( p = 0.02), respectively. For HOMA-IR, we detected associations with TCF-2 , ADAM30 and CDKN2A/B , with β values of 0.05 ( p = 0.04), −0.07 ( p = 0.03) and −0.08 ( p = 0.02), respectively. We also found significant associations of ADAM30 ( β = −0.05; p = 0.01) and CDKN2A/B ( β = −0.05; p = 0.03) with HOMA-β. THADA variant (rs7578597) was associated with type 2 diabetes (OR 1.5; 95% CI 1.04, 2.22; p = 0.03). Conclusions/interpretation We validated the association of seven established loci with intermediate traits related to type 2 diabetes in an Indian population using a design resistant to population stratification.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0012-186X 1432-0428
DOI:	10.1007/s00125-011-2355-6