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.
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.
Gupta
Vipin
V
South Asia Network for Chronic Disease, Public Health Foundation of India, Delhi-110016.
Khadgawat
Rajesh
R
Ng
Hon Keung Tony
HK
Kumar
Satish
S
Aggarwal
Ajay
A
Rao
Vadlamudi Raghavendra
VR
Sachdeva
M P
MP
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
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