肿瘤坏死因子基因多态性在慢性乙型肝炎患者中的分布

Association between the tumor necrosis factor gene polymorphisms and the clinical types of patients with chronic hepatitis B virus infection

目的探讨肿瘤坏死因子(TNF)基因多态性与慢性乙型肝炎病毒(HBV)感染者临床类型之间的关系。方法运用聚合酶链反应限制性片段长度多态性(PCRRFLP)分析的方法检测TNFα基因启动子区308位和TNFβ基因第一内含子252位的单个核苷酸多态性(SNPs)在不同临床类型的慢性HBV感染者及健康对照者中的分布频率,并用放射免疫法测定其血清TNFα浓度。结果56例慢性重型乙型肝炎患者(CSHB)中TNF1/2基因型频率及TNF2等位基因频率均显著高于健康对照组(90例)(25%vs11.1%,P=0.028;12.5%vs5.6%,P=0.036)和慢性轻度乙型肝炎及无症状携带者(AsC)组(71例)(25%vs8.5%,P=0.011;12.5%vs4.2%,P=0.015),且CSHB患者中,TNF1/2杂合子的血清TNFα及胆红素(TBiL)水平明显高于TNF1/1纯合子(P<0.05)。CSHB组与健康对照组的TNFβ2/2基因型及TNFβ2等位基因分布差异无统计学意义,而慢性轻度乙型肝炎患者及AsC组的TNFβ2/2基因型频率显著低于健康对照组(9.9%vs24.4%,P=0.043)和CSHB组(9.9%vs26.8%,P=0.043)。结论TNF基因多态性与HBV感染者的临床类型有关,可能为其宿主因素之一。

Objective To explore whether the polymorphisms within the tumor necrosis factor alpha (TNF-α) and TNF-β gene are associated with the clinical types of patients with chronic hepatitis B virus (HBV) infection. Methods By using a restriction fragment length polymorphism (RFLP) assay of polymerase chain reaction (PCR) products, the single nucleotide polymorphisms (SNPs) within TNF-α and TNF-β gene among 56 patients with chronic severe hepatitis B and 71 patients with chronic mild hepatitis B or asymptomatic carriers as well as 90 healthy controls were analyzed. The TNF-α concentration of serum in 56 patients with chronic severe hepatitis B and 30 healthy controls were determined by radio immunity assay (RIA). Results The frequencies of the TNF1/2 genotype and the TNF2 allele were significantly increased in patients with chronic severe hepatitis compared with healthy controls (25% vs 11.1%,P=0.028;12.5% vs 5.6%,P=0.036) and patients with chronic mild hepatitis B and asymptomatic carriers (25% vs 8.5%,P=0.011;12.5% vs 4.2%,P=0.015). Furthermore, heterozygotes carrying TNF2 allele had significantly higher levels of serum TNF-α than homozygotes for the wild type allele among all patients with chronic severe hepatitis B (P<0.05). The genotype distribution and allele frequency of TNF-β were similar between patients with chronic severe hepatitis B and healthy controls. However, the frequency of TNF-β~*2/2 genotype in patients with chronic mild hepatitis B and asymptomatic carriers was significantly lower than in control subjects ( 9.9% vs 24.4%,P= 0.043) and patients with chronic severe hepatitis B ( 9.9% vs 26.8%,P= 0.043).Conclusions TNF gene polymorphisms were associated with the clinical types of patients with chronic HBV infection and may play an important role in the progress of HBV infection as one of the host factor.