| | | TNF-α基因单核苷酸多态性与HBV感染结局
| | 西医学 评职论文【关键词】 ,乙型肝炎；TNF-α基因；单核苷酸多态性（SNPs）；单体型
摘要： 目的西医学 评职论文 探讨肿瘤坏死因子α（TNFα）基因启动子区238G/A、-857T/C、-863C/A与乙型肝炎病毒（HBV）感染结局之间的西医学 评职论文关系。方法 采用病例-对照研究方法，募集244例HBV自限性感染者、212例HBsAg携带者和391例慢性乙型肝炎患者作为研究对象，应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，对（TNF-α）基因启动子区-238G/A、-857C/T、-863C/A基因型进行测定。结果 自限性感染者携带-238A等位基因的频率显著低于HBsAg携带者（P=0.04）和慢性乙肝患者（P=0.047）；慢性乙肝患者携带TNF-α-857C等位基因的频率显著高于HBsAg携带者（P=0.0008）和自限性感染者（P=0.03）；慢性乙肝者TNF-α-863A等位基因频率显著高于HBsAg携带者（P=0.02）。应用多元Logistic回归分析，控制年龄、性别等混杂因素后，慢性乙肝患者与HBV自限性感染者比较，TNF-α-857CC和TNF-α-238 GA与慢性乙肝显著关联（OR=1.53,P=0.044;OR=2.11，P=0.045）；慢性乙肝患者与HBsAg携带者比较，TNF-α-857CC与慢性乙肝显著关联（OR=1.92,P=0.004）；HBsAg携带者与HBV自限性感染者比较，TNF-α-238GA与HBsAg携带者显著关联（OR=2.34,P=0.020）。结论 TNF-α基因启动子区多态性可能是影响HBV感染结局的重要危险因素。
关键词： 乙型肝炎；TNF-α基因；单核苷酸多态性（SNPs）；单体型
Relationship between polymorphisms of TNF-α gene promoter region and HBV infection outcome
Abstract： Objective To determine whenther -238G/A,-857T/C and -863C/A polymorphisms of tumor necrosis factor-alphya (TNF-α) gene promoter were associated with outcomes of hepatitis B virus (HBV) infection.Methods A total of 244 HBV self-limited infected subjects,212 asymptomatic HBsAg carriers (HBsAg carriers) and 391 chronic hepatitis B (HB) patients were recruited to conduct a case-control study.TNF-α-238G/A,-857C/T and -863C/A gene promoter polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Results The frequency of -238 allele A in self-limited individuals was 2.6%,significantly lower than 5.0% in chronic HB patients and 5.3% in HBsAg carriers (P=0.04 and P=0.047),respectively.The frequency of TNF-α-857 allele C in chronic HB patients was 87.5%,significantly higher than 80.5% in HBsAg carriers and 82.8% in self-limited individuals (P=0.0008 and P=0.03),respectively.The frequency of TNF-α-863 allele A in chronic HB group was 77.5%,significantly higher than 71.5% in HBsAg carriers (P=0.02).Multiple logistic regression analyses indicated an increased risk of chronic HB associated with TNF-α-238GA and -857CC after gender and age adjusting (OR=1.53,P=0.044;OR=2.11,P=0.045),and HBsAg carriers with -857CC significantly increasing risk of chronic HB associated with TNF-α -238GA and -857CC after gender and age adjusting (OR=1.53,P=0.044;OR=2.11,P=0.045),an HBsAg carriers with -857CC significantly increasing risk of chronic HB(OR=1.92,P=0.004),and -238GA associated with and increasing risk of HBsAg carriers (OR=2.34,P=0.020).Conclusion TNF-α promoter polymorphism is probably an important risk factor of the influence of outcome of HBV infection.
Key words： hepatitis B;tumor nectosis factor-alpha(TNF-α)gene;single nucleotide polymorphisms(SNPs);genotype
乙型肝炎的治疗是亟待解决的全球性公共卫生问题〔1〕。感染乙型肝炎病毒(HBV)后可产生自限性感染、HBsAg携带者、慢性乙肝多种不同临床结局。HBV感染结局多样性一直是研究者关注的问题，从遗传易感性角度探讨其原因是一个重要研究方向。细胞因子在抵抗病毒感染中起重要作用，它能够间接和直接抑制病毒复制〔2〕。肿瘤坏死因子α（TNF-α）的转录水平与TNF-α启动子区单核苷酸多态性有关〔3〕。本研究比较了TNF-α启动子区-238G/A、-857C/T及-863C/A基因型在自限性感染、HBsAg携带状态和慢性乙肝3种不同HBV感染结局者中分布频率的差异，探讨TNF-α基因多态性与HBV感染结局关系。
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