title: Association of IRS1, CAPN10, and PPARG gene polymorphisms with type 2 diabetes mellitus in the high-risk population of Hyderabad, India.
abstract: BACKGROUND
  We attempted to validate earlier findings on the nature of the association of the IRS1, CAPN10, and PPARG genes with type 2 diabetes mellitus (T2DM) in the high-risk population of Hyderabad, India.
  
  
  METHODS
  A sample of 1379 subjects (758 T2DM patients, 621 controls) was genotyped for single nucleotide polymorphisms (SNPs) of the IRS1 (rs1801278), CAPN10 (rs3792267, rs5030952), and PPARG (rs1801282) genes.
  
  
  RESULTS
  The allele and genotype frequencies of IRS1 (rs1801278) and CAPN10 (rs3792267) SNPs differed significantly between the patient and control groups. Logistic regression analysis suggested a significant association of these two SNPs (P ≤ 0.007) with T2DM and the strength of association did not alter when adjusted for age, gender, body mass index, and the waist : hip ratio as covariates. The same two SNPs showed significant association in multivariate logistic regression analyses, even after Bonferroni correction for multiple testing, suggesting an independent nature of the role of these genes in the manifestation of T2DM in our population.
  
  
  CONCLUSIONS
  We replicated the significant association of rs1801278 and rs3792267 SNPs of the IRS1 and CAPN10 genes with T2DM in the population of Hyderabad. Despite the known biological significance of the PPARG gene and a sufficient statistical power of the present study, we could not replicate the association of PPARG with T2DM in our high-risk population. Given the vast ethnic, geographic, and genetic heterogeneity of the Indian population, many more studies are needed covering the ethnic and geographic heterogeneity of India to enable identification of an Indian-specific profile of genes associated with T2DM.
authors.affiliation: Biological Anthropology Unit (Molecular Anthropology Group), Indian Statistical Institute, Hyderabad, India.
authors.forename: Uma Jyothi
authors.initials: UJ
authors.lastname: Kommoju
authors.forename: Jayaraj
authors.initials: J
authors.lastname: Maruda
authors.forename: Subburaj
authors.initials: S
authors.lastname: Kadarkarai Samy
authors.forename: Kumuda
authors.initials: K
authors.lastname: Irgam
authors.forename: Jaya Prasad
authors.initials: JP
authors.lastname: Kotla
authors.forename: Battini Mohan
authors.initials: BM
authors.lastname: Reddy
mesh_terms: D000483:Alleles; D015992:Body Mass Index; D002154:Calpain / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007194:India; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D047495:PPAR gamma; D002154:Calpain; C415197:calpain 10
keywords: Hyderabad (India); genetic association; population; single nucleotide polymorphism; type 2 diabetes mellitus; 关键词：遗传相关性，海得拉巴（印度），人群，单核苷酸多态性，2型糖尿病