中国汉族人群尼古丁依赖的易感基因位点关联分析及易感基因功能研究

项目名称： 中国汉族人群尼古丁依赖的易感基因位点关联分析及易感基因功能研究

项目编号： No.81201034

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 张学伟

作者单位： 中南大学

项目金额： 23万元

中文摘要： 遗传因素可能在吸烟行为中起着重要作用。多项欧美国家的全基因组关联研究（Genome-wide association studies, GWAS）及元分析（meta analysis）鉴定了某些与吸烟关联的SNPs，表明不同基因与吸烟行为相关。本项目拟通过对中国汉族吸烟人群与多个尼古丁依赖易感基因的关联分析，验证中国人群中与尼古丁依赖相关的基因；同时对多个基因进行研究，可能发现其中有最强相关的易感基因，并为解释尼古丁依赖的病因学、寻找干预和治疗的靶点提供线索。另一方面，BDNF基因rs6265位点已被证实与吸烟起动有较强关联，本项目拟通过检测中国汉族吸烟人群血清中BDNF蛋白表达水平与rs6265等位基因的关联，以及不同等位基因型经尼古丁处理后BDNF基因甲基化水平、蛋白表达水平、细胞电生理等的变化，探讨rs6265位点在中国人群中与吸烟起动的关联以及可能影响BDNF基因功能的分子机制。

中文关键词： 吸烟；尼古丁依赖；易感位点；多态；关联分析

英文摘要： Consist but indirect evidence has implicated genetic factors in smoking behavior.Previous genome-wide association studies(GWAS)and GWAS meta analyses in european and american crowd identified multiple loci associted with smoking behavior.Notely,the several loci identified were each associated with only one specific smoking phenotype.The findings suggests that separate genetic loci contribute modestly to phenotypic variability in each aspect of smoking behavior.We propose to identify multiple susceptibility loci as being associated with smoking behavior in Chinese Han group.The findings will identify possiblely the strongest associatied loci with nicotine dependence of Chinese,which,in turn,may have implications for the way in which smoking cessation therapies and tobacco control efforts are designed and targeted.The missense variant rs6265 located in BDNF exceeded genome wide significence for smoking initiation.We designed three aspects experiment to investigate the molecular mechanisms of nicotine dependence.The first, We proposed to detected the expression level of the BDNF protein in serum, the second, measure the level of DNA methylation of BDNF from primary cultured hippocampus neurons after treated by nicotine, the finally, electrophysiological change of primary cultured hippocampus neurons which by thra

英文关键词： smoking；nocotine dependence；susceptibility loci；polymorphism；associated study