TNF-α启动子区基因多态性与SARS易感性及症状关系研究

Study on the roles of TNF-α gene polymorphism at the promoter region in the susceptibility and symptom of SARS coronavirus infection

【目的】研究TNF-α基因多态性在严重急性呼吸道综合征(sever acute respiratory syndrome,SARS)发生中的作用。【方法】采用病例对照研究设计,采用PCR-SBT(PCRsequencing basedtyping)方法检测75例SARS康复人员、41例医护人员和92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,分析TNF-α基因多态性与SARS症状的关系。进行TNF-α启动子区基因多态性检测,运用SPSS 11.5进行统计结果分析。【结果】TNF-α启动子区基因多态性位点有-1 031、-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。在这些多态性位点中,-204位点的基因多态性在SARS康复人员和健康人员中存在差别(χ2=4.20,P=0.04),突变基因型(CT)可能为SARS-Cov感染的保护基因型(OR=0.95,95%CI0.90～0.99),未见其他多态性位点在该三人群分布差别。-308位点G和A等位基因在SARS康复人员和健康人员分布不一致,SARS人群的A等位基因显著高于对照人群(χ2=8.96,P=0.003)。同时,未见TNF-α启动子区基因多态性与SARS临床症状之间关联。等位基因分析也未见差别。【结论】TNF-α启动子区-204位点的T→C改变可能减少SARS的发生风险,而-308位点A等位基因可能是SARS发生的风险之一。而TNF-α启动子区基因多态性与SARS的临床症状程度无关。

[ Objective] To study the roles of TNF-α gene polymorphism in the susceptibility and symptom of SARS coronavirus infection. [Methods] Case-control design was used to study the association between genetic polymorphisms of TNF-α at the promoter region including 75 recovered SARS patients, 41 health care workers and 92 healthy controls. Case-case control desisn was used to study the association of this gene locus polymorphisms with the symptom of SARS. PCR sequencing based typing （PCR- SBT） method was used to determine the polymorphisms of TNF-α at the promoter region and data were analyzed using SPSS11.0 software. [ Results] The detennined TNF-α gene at locus of the promoter region polymorphism sites including six previous reported SNPs [ - 1031 （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 significant difference between the - 204 genotype frequency in the SAILS and the control （χ^2 = 4.20, P = 0.04） and the CT genotype may be the protective genotype against SARS - Cov infection （OR = 0.95, 95% 01 0.90 - 0.99）. No obvious difference was observed in other SNPs. However, the allele frequency of - 308 A showed a higher rate in the SARS patients than that in the control （χ^2 = 8.96, P = 0.003）. At the same time, no obvious association was observed with the symptom of SARS according to genotype and allele analyzing. [ Conclusions] The CT/CC genotype of - 204 may lower the risk of getting SARS-Cov infection yet the A allele at - 308 may increase that risk. And there may be no association between the SAPS symptom with the polymorphisms of TNF-α gene at the promoter region.