TNF-α基因启动子区多态性与SARS发生关系的连锁不平衡研究  

Study on the linkage disequilibrium of TNF-α gene polymorphism at the promoter region in the occurrence and progress of SARS coronavirus infection

作　　者：魏茂提[1] 张克菊[2] 何丽[2] 韩燚[2] 杨震[2] 惠武利[1] 胡役兰[1] 王世鑫[2] 

机构地区：[1]武警医学院流行病学教研室,天津300162 [2]武警医学院蛋白质组学实验室,天津300162

出　　处：《中国免疫学杂志》2008年第10期911-916,共6页Chinese Journal of Immunology

基　　金：天津市科技攻关重点项目(05YFSZSF02900);武警医学院院级项目(WY-2005-14)资助

摘　　要：目的:研究TNF-α启动子区基因多态性连锁不平衡与严重急性呼吸道综合征(Sever acute respiratory syndrome,SARS)发生关系。方法:采用病例对照研究设计,检测75例SARS康复人员和95例健康人员的TNF-α基因启动子区多态性,分析TNF-α基因启动子区多态性位点的连锁作用与SARS-Cov易感性关系;在SARS康复病人中采用病例-病例对照研究设计,研究TNF-α基因多态性位点的连锁作用与SARS临床症状的关系。采用PCR-SBT(PCR Sequencing Based Typing)方法进行TNF-α启动子区基因多态性检测,运用LDA分析软件完成(Linkage Disequilibrium Analyzer Ver1.0,Chinese national human genome center,Beijing,China)进行多态性位点的连锁作用分析,采用Phase软件(http://www.stat.washington.Edu/stephens,v2.1.1)进行单倍体型分析。结果:PCR-SBT方法可以成功获得TNF-α启动子区基因多态性,检测出的多态性位点有-1031、-863、-857、-572、-308、-238、-204和-163,其中-572(A>C)和-204(T>C)为新发现多态性位点。单倍体型分析结果显示,SARS组和对照组主要以Hap(T;C;C;A;G;G;T;G)、Hap(C;A;C;A;G;G;T;G)、Hap(T;C;T;A;G;G;T;G)和Hap(C;C;C;A;G;A;T;G)为主,但两组人群的单倍体型分布频率无显著差别(P=0.30)。对照人群的连锁模式可能不同于SARS人群,对照组-857(C>T)和-572(A>C)分别与-308(G>A)存在连锁关系,而SARS组不存在该位点的连锁,但存在-238(G>A)与-163(G>A)连锁关系。轻症组和重症组主要以Hap(T;A;C;A;G;G;T;G)、Hap(T;A;T;A;G;G;T;G)、Hap(C;C;C;A;G;G;T;G)和Hap(C;A;C;A;G;A;T;G)为主,两组人群的单倍体型分布频率无显著差别(P=0.39)。重症SARS的-857(C>T)与-308(G>A)也存在连锁关系,而轻症SARS不存在该连锁关系。结论:TNF-α基因启动子区的连锁不平衡可能与SARS的发生及进展相关联。Objective：To study the linkage disequilibrium of TNF-α gene polymorphism in the occurrence and the progress of SARS coronavirus infection.Methods：Case-control designation was used to study the association between genetic linkage disequilibrium of TNF-α polymorphisms at the promoter region including 75 recovered SARS patients,41 health care workers and 95 healthy control.Case-case control study was used to study the association of the linkage disequilibrium TNF-α gene polymorphisms with the symptoms of SARS.PCR sequencing based typing （PCR-SBT） method was used to determine the polymorphisms of TNF-α at the promoter region and the data were analyzed using LDA（Linkage Disequilibrium Analyzer Ver1.0,Chinese national human genome center,Beijing,China）and Phase（http：www.stat.washington.Edu /steph-ens,v2.1.1）.Results：It is successful to get the polymorphisms of TNF-αgene at locus of the promoter region using PCR-SBT method and the determined polymorphism sites including six previous reported SNPs [-1 031（T〉C）,-863（C〉A）,-857（C〉T）,-308（G〉A）,-238（G〉A） and -163（G〉C）] and two newly discovered SNPs [-572（A〉C）and -204（T〉C）].There was no association between the SARS and the control of haplotypes and four main haplotypes was observed in these two groups including Hap（T;C;C;A;G;G;T;G）,Hap（C;A;C;A;G;G;T;G）,Hap（T;C;T;A;G;G;T;G） and Hap（C;C;C;A;G;A;T;G）.There was linkage of -238（G〉A）and -163（G〉A） of the polymorphism in the SARS group instead of the -857（C〉T）and -572（A〉C）with -308（G〉A） in the control group.There was no association between the SARS severity with haplotypes（P=0.39） and four main haplotypes was observed in these two groups including Hap（T;A;C;A;G;G;T;G）,Hap（T;A;T;A;G;G;T;G）,Hap（C;C;C;A;G;G;T;G） and Hap（C;A;C;A;G;A;T;G）.There was linkage of 857（C〉T）and -308（G〉A） in serve SARS patients instead of in the light SARS.Conclusion：The linkage disequilibrium may be attributed to

关 键 词：TNF-Α基因 基因多态性 连锁不平衡 SARS 启动子区 

分 类 号：R135.2[医药卫生—劳动卫生]