title: A validation study of type 2 diabetes-related variants of the TCF7L2, HHEX, KCNJ11, and ADIPOQ genes in one endogamous ethnic group of north India.
abstract: The aim of this study was to validate the single nucleotide polymorphisms (SNPs) of four candidate genes (TCF7L2, HHEX, KCNJ11, and ADIPOQ) related to type 2 diabetes (T2D) in an endogamous population of north India; the Aggarwal population, having 18-clans. This endogamous population model was heavily supported by recent land mark work and we also verified the homogeneity of this population by clan-based stratification analysis. Two SNPs (rs4506565; rs7903146) in TCF7L2 were found to be significant (p-value = 0.00191; p-value = 0.00179, respectively), and odds ratios of 2.1 (dominant-model) and 2.0 (recessive-model) respectively, were obtained for this population. The TTT haplotype in the TCF7L2 gene was significantly associated with T2D. Waist-Hip ratio (WHR), systolic blood pressure (SBP), and age were significant covariates for increasing risk of T2D. Single-SNP, combined-SNPs and haplotype analysis provides clear evidence that the causal mutation is near to or within the significant haplotype (TTT) of the TCF7L2 gene. In spite of a culturally-learned sedentary lifestyle and fat-enriched dietary habits, WHR rather than body-mass-index emerged as a robust predictor of risk for T2D in this population.
authors.affiliation: South Asia Network for Chronic Disease, Public Health Foundation of India, Delhi-110016.
authors.forename: Vipin
authors.initials: V
authors.lastname: Gupta
authors.forename: Rajesh
authors.initials: R
authors.lastname: Khadgawat
authors.forename: Hon Keung Tony
authors.initials: HK
authors.lastname: Ng
authors.forename: Satish
authors.initials: S
authors.lastname: Kumar
authors.forename: Ajay
authors.initials: A
authors.lastname: Aggarwal
authors.forename: Vadlamudi Raghavendra
authors.initials: VR
authors.lastname: Rao
authors.forename: M P
authors.initials: MP
authors.lastname: Sachdeva
mesh_terms: D052242:Adiponectin / Q000235:genetics; D000328:Adult; D000367:Age Factors; D000368:Aged; D001786:Blood Glucose / Q000235:genetics; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D012306:Risk; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000235:genetics*; D049629:Waist-Hip Ratio; D000099161:Kcnj11 Channel
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D018398:Homeodomain Proteins; D024661:Potassium Channels, Inwardly Rectifying; D051820:TCF Transcription Factors; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D000099161:Kcnj11 Channel; C499918:ADIPOQ protein, human; C078492:HHEX protein, human; C544894:TCF7L2 protein, human