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

• 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
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-011-2355-6

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.