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目的 研究慢性乙型肝炎病毒(HBV)感染者肿瘤坏死因子α(TNFα)-308位点的基因多态性与HBV C基因区突变的关系.方法 对95例慢性HBV感染者进行研究,采用聚合酶链反应.限制性片断长度多态性(PCR-RFLP)技术分析患者TNFα-308位点的多态性.对PCR产物直接测序,检测HBV C基因区nt1762/1764、nt1896、nt1899、nt1862、aa60、as87及aa97位点是否存在突变.采用Fisher's精确概率法比较TNFα-308位点不同基因型患者HBV C基因区常见突变的检出率.结果 TNFα-308位点共发现3种多态性,分别为G/G型63例(63/95,66.3%),G/A型28例(28/95,29.5%),A/A型4例(4/95,4.2%).TNFα-308位点G/G、G/A、A/A基因型患者HBV C基因区aa87位点及as97位点突变型检出率均分别为39.3%(24/61)、11.5%(3/26)和50.0%(2/4),差异有统计学意义(F=7.658,P<0.05);而nt1762/1764、nt1896、nt1899、nt1862以及aa60位点突变型检出率比较差异无统计学意义(F值分别为0.669、1.542、1.123、2.420和0.966,P值均>0.05).结论 慢性HBV感染者TNFα-308位点G/A基因型相对于G/G基因型不易发生HBV抗原性变异,有利于HBV的清除.

Objective To investigate the association between polymorphism of TNFα-308 and mutations of HBV C region in patients with chronic HBV infection. Methods Ninety-five patients with chronic HBV infection were recruited in the study. The single nucleotide polymorphism(SNP) of TNFα-308 Was determined by restriction fragment length polymorphism(RFLP). Mutations of nt1762/1764, nt1896, nt1899, nt1862, as60, aa87 and as97 in HBV C region were detected by direct sequencing after PCR amplification. Mutations of the above points among different genotypes were compared by Fisher's exget test. Results Three different genotypes G/G(63/95, 66.3%), G/A(28/95, 29.5%) and A/A(4/95, 4.2%) were found in TNFα-308 site. The rates of mutations of aa87 and aa97 points in patients with G/G, G/A and A/A genotype were 39.3%(24/61), 11.5%(3/26) and 50.0% (2/4), respectively(F=7.658, P<0.05);while the mutation rates of nt1762/1764, nt1896, nt1864, nt1899 and aa60 were of no statistical significance among different genotypes(F=0.669, 1.542, 1.123, 2.420 and 0.966, P>0.05). Conclusion Compared with G/G genotype, antigenicity of HBV may be more stable in patients with TNFα-308 G/A genotype, which is beneficial to HBV clearance.