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 the cause and the progress of SARS.
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
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