Gupta Vipin, Khadgawat Rajesh, Ng Hon Keung Tony, Kumar Satish, Aggarwal Ajay, Rao Vadlamudi Raghavendra, Sachdeva M P
South Asia Network for Chronic Disease, Public Health Foundation of India, Delhi-110016.
Ann Hum Genet. 2010 Jul;74(4):361-8. doi: 10.1111/j.1469-1809.2010.00580.x.
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.
本研究的目的是在印度北部一个有18个氏族的内婚制人群——阿加瓦尔人群中，验证与2型糖尿病（T2D）相关的四个候选基因（TCF7L2、HHEX、KCNJ11和ADIPOQ）的单核苷酸多态性（SNP）。这种内婚制人群模型得到了近期具有里程碑意义的研究的大力支持，我们还通过基于氏族的分层分析验证了该人群的同质性。发现TCF7L2基因中的两个SNP（rs4506565；rs7903146）具有显著性（p值分别为0.00191；0.00179），该人群在显性模型下的优势比为2.1，隐性模型下的优势比为2.0。TCF7L2基因中的TTT单倍型与T2D显著相关。腰臀比（WHR）、收缩压（SBP）和年龄是T2D风险增加的显著协变量。单SNP、组合SNP和单倍型分析提供了明确的证据，表明因果突变接近或位于TCF7L2基因的显著单倍型（TTT）内或其中。尽管存在文化习得的久坐生活方式和富含脂肪的饮食习惯，但在该人群中，腰臀比而非体重指数成为T2D风险的有力预测指标。
