LMP2/LMP7基因多态性与乙型肝炎病毒感染结局的关系

Association between LMP2/ LMP7 gene polymorphisms and outcome of hepatitis B virus infection

目的:探讨低相对分子质量蛋白酶体(LMP)基因单核苷酸多态性(SNP)与HBV感染结局之间的关联.方法:提取287例HBV持续感染者(包括无症状HBV携带者、慢性乙型肝炎及乙型肝炎后肝硬化患者)及278例健康对照外周血基因组DNA,用PCR-RFLP方法分析LMP2/LMP7基因Codon60/Codon145两个多态性位点的基因型.结果:LMP7基因多态性位点在健康对照与无症状HBV携带者之间的差异有统计学意义(P<0.05),与携带Gln/Gln基因型者比较,携带Gln/Lys基因型者乙型肝炎患病风险增加3.35倍(95%CI:2.02-5.58),携带Lys/Lys基因型者乙型肝炎患病风险增加3.46倍(95%CI:1.41-8.48),携带至少1个Lys等位基因者(即Gln/Lys和Lys/Lys基因型)乙型肝炎患病风险增加3.37倍(95%CI:2.06-5.52);;LMP7基因多态性位点在健康对照与进展性肝炎(包括慢性乙型肝炎和肝硬化)患者之间的差异有统计学意义(P<0.05),与携带Gln/Gln基因型者比较,携带Gln/Lys基因型者乙型肝炎患病风险增加2.22倍(95%CI:1.48-3.32),携带Lys/Lys基因型者乙型肝炎患病风险增加4.33倍(95%CI:2.15-8.73),携带至少1个Lys等位基因者(即Gln/Lys和Lys/Lys基因型)乙型肝炎患病风险增加2.49倍(95%CI:1.69-3.65);;LMP2/LMP7基因多态性位点在无症状HBV携带者与进展性肝炎患者间的差异无统计学意义(P>0.05).结论:LMP7基因可能是无症状HBV携带和进展性肝炎的易感基因;;LMP基因多态性与HBV感染的结局可能无明显相关性.

AIM： To investigate the possible association between LMP2/LMP7 gene polymorphisms and outcome of hepatitis B virus （HBV） infection. METHODS： Peripheral blood leukocytes were isolated from 287 patients with persistent HBV infection, including 100 asymptomatic HBV carriers （AsC group） and 187 patients with active liver diseases such as chronic hepatitis B andliver cirrhosis （ALD group）, and 278 healthy volunteers for extraction of genomic DNA. LMP gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. RESULTS： The prevalence of LMP7 codon 145 Gln/Lys heterozygote, Lys/Lys homozygote, and Gln/Lys plus Lys/Lys genotypes was signif icantly higher in the AsC group than in healthy controls （OR = 3.35, 3.46 and 3.37; 95%CI： 2.02-5.58, 1.41-8.48 and 2.06-5.52; all P 0.001）. Similarly, the prevalence of LMP7 codon 145 Gln/Lys heterozygote, Lys/Lys homozygote, and Gln/Lys plus Lys/Lys genotypes was signif icantly higher in the ALD group than in healthy controls （OR = 2.22, 4.33 and 2.49; 95%CI： 1.48-3.32, 2.15-8.73 and 1.69-3.65; all P 0.001）. However, there was no signif icant difference in LMP2/LMP7 polymorphisms between the AsC and ALD groups. CONCLUSION： The LMP7 gene polymorphisms may be associated with susceptibility to asymptomatic HBV infection and active liver diseases, but not with the clinical outcome of persistent HBV infection.