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目的探讨肿瘤坏死因子-α(TNF-α)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-238 A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。
Objective To investigate the relationship between TNF-α gene promoter region-238G / A-, 857T / C-, 863C / A and hepatitis B virus (HBV) infection. Methods A case-control study was conducted in which 244 patients with self-limited HBV infection, 212 HBsAg carriers and 391 patients with chronic hepatitis B were enrolled in this study. Polymerase chain reaction-restriction fragment length polymorphism -RFLP) were used to detect the -238G / A, -857C / T and -863C / A genotypes of TNF-α gene promoter region. Results The frequency of carrying -238 A allele was significantly lower in patients with self-limited infection than those with HBsAg carriers (P = 0.04) and chronic hepatitis B (P = 0.047). The frequency of TNF-α-857C alleles in patients with chronic hepatitis B The frequency of TNF-α-863A allele in chronic hepatitis B patients was significantly higher than that in HBsAg carriers (P = 0.0008) and self-limiting patients (P = 0.03). Using multivariate logistic regression analysis and control of confounders such as age and sex, TNF-α-857CC and TNF-α-238 GA were significantly associated with chronic hepatitis B (OR = 1.53, P (OR = 1.92, P = 0.004); HBsAg carriers and HBV self-limited infection In comparison, TNF-α-238GA was significantly associated with HBsAg carriers (OR = 2.34, P = 0.020). Conclusion TNF-α gene promoter polymorphism may be an important risk factor for the outcome of HBV infection.