六个II型糖尿病易感基因座和一个FTO变体对巴基斯坦人群肥胖的影响。
Effect of six type II diabetes susceptibility loci and an FTO variant on obesity in Pakistani subjects.
作者信息
Ullah Shahid Saleem, Wah Li Ka, Acharya Jayshree, Cooper Jackie A, Hasnain Shahida, Humphries Stephen E
机构信息
Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan.
Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, The Rayne Building, Institute of Cardiovascular Sciences, University College London, London, UK.
出版信息
Eur J Hum Genet. 2016 Jun;24(6):903-10. doi: 10.1038/ejhg.2015.212. Epub 2015 Sep 23.
The aim of the current study was to analyze the effect of six type II diabetes GWAS loci rs3923113 (GRB14), rs16861329 (ST6GAL1), rs1802295 (VPS26A), rs7178572 (HMG20A), rs2028299 (AP3S2) and rs4812829 (HNF4A), and an FTO polymorphism (rs9939609) on obesity. The probable mechanism of action of these SNPs was analyzed by studying their association with various biochemical and anthropometric parameters. A total of 475 subjects (obese=250, controls=225) were genotyped by TaqMan assay and their lipid profile was determined. Allele/genotype frequencies and an unweighted/weighted gene score were calculated. The effect of the gene score on anthropometric and biochemical parameters was analyzed. The minor allele frequencies of all variants were comparable to that reported in the original studies and were associated with obesity in these Pakistani subjects. Subjects with 9 risk alleles differ from those with <3 and overall there is no significant effect (P-value for trend 0.26). None of the SNPs were associated with any of the serum lipid traits. We are the first to report the association of these T2D SNPs with obesity. In the Pakistani population the reported effect of six SNPs for obesity is similar to that reported for T2D and having a combination of risk alleles on obesity can be considerable. The mechanism of this effect is unclear, but appears not to be mediated by changing serum lipid chemistry.
本研究的目的是分析6个2型糖尿病全基因组关联研究（GWAS）位点rs3923113（GRB14）、rs16861329（ST6GAL1）、rs1802295（VPS26A）、rs7178572（HMG20A）、rs2028299（AP3S2）和rs4812829（HNF4A）以及一个FTO基因多态性（rs9939609）对肥胖的影响。通过研究这些单核苷酸多态性（SNP）与各种生化和人体测量参数的关联，分析了它们可能的作用机制。采用TaqMan分析法对475名受试者（肥胖者=250名，对照组=225名）进行基因分型，并测定其血脂谱。计算等位基因/基因型频率以及未加权/加权基因评分。分析基因评分对人体测量和生化参数的影响。所有变异的次要等位基因频率与原始研究报道的频率相当，且与这些巴基斯坦受试者的肥胖相关。具有9个风险等位基因的受试者与具有<3个风险等位基因的受试者不同，总体上没有显著影响（趋势P值为0.26）。没有一个SNP与任何血清脂质特征相关。我们是首个报道这些2型糖尿病SNP与肥胖关联的研究。在巴基斯坦人群中，所报道的6个SNP对肥胖的影响与对2型糖尿病的影响相似，并且具有风险等位基因组合对肥胖的影响可能相当大。这种影响的机制尚不清楚，但似乎不是由血清脂质化学变化介导的。
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