preS／S区基因变异与隐匿性HBV感染的关系

摘要

目的：初步探讨HBV preS／S区基因变异与隐匿性HBV感染（ OBI ）、肝脏损伤的关系。方法收集116例HBsAg阴性（从乙型肝炎康复患者中选取）及102例HBsAg阳性患者的血清进行 DNA提取，使用巢式PCR对针对preS／S区、pre-core／core区及X基因区进行检测，确定OBI例数，并对克隆标本的preS／S区全长基因进行测序分析，分别对比OBI患者和HBsAg患者、伴有严重肝损伤的OBI患者和HBsAg阳性患者的preS／S区基因序列。结果 OBI检出率为60．34％（70／116），OBI患者M1I、Q2K、Q129N／R／P、S210R及G185R的突变频率均明显高于HBsAg阳性患者（P＜0．05），OBI患者的preS缺失率亦高于HBsAg阳性患者（P＜0．05）；伴有严重肝损伤的OBI患者Q129N／R／P突变频率及preS缺失率与伴有严重肝损伤HBsAg阳性患者比较，差异无统计学意义（P＞0．05），但M1I、Q2K、S210R及G185R突变频率均明显高于均明显高于伴有严重肝损伤HBsAg阳性患者（P＜0．05）。结论 M1I、Q2K、Q129N／R／P、S210R及G185R的突变及preS缺失对诊断OBI有一定的指导作用，当患者存在肝损伤时Q129N／R／P变异及preS缺失对诊断OBI的指导作用可能受影响。%Objective To preliminarily investigate the relationship of genetic variation of HBV preS /S region with occult hepatitis B virus infection(OBI) or hepatic damage.Methods One hundred and sixteen cases of negative HBsAg selected from hepatitis B patients and 102 cases of positive HBsAg were enrolled in the study .Their serum samples were obtained for DNA extraction .The regions of preS/S, pre-core/core and X gene were detected using nested PCR for confirming OBI .The samples of cloned pres/S gene were sequenced ,and a comparison of pres/S gene sequence was conducted between patients with OBI and with HBsAg ,as well as between patients with OBI and severe hepatic damage and patients with positive gene and severe hepatic damage.Results The detection rate of OBI was 60.34%(70/116). OBI patients owned significantly higher mutation frequencies of M1I,Q2K,Q129N/R/P,S210R and G185R as well as a higher deletion rate of preS compared to the patients with positive HBsAg(P<0.05).There was no significant difference in the mutation frequency of Q129N/R/P or deletion rate of preS between OBI patients with severe hepatic damage and patients with positive HBsAg and severe hepatic damage (P>0.05). But patients with OBI and severe hepatic damage had significantly higher mutation frequencies of M1I,Q2K,S210R and G185R compared to patients with positive HBsAg and severe hepatic damage (P<0.05).Conclusion The mutation of M1I,Q2K ,Q 129N/R/P,S210R and G185R as well as the preS deletion is valuable for diagnostic guidance in OBI .However,the guidance of Q129N/R/P mutation and preS deletion in the diagnosis of OBI might be affected when patients suffer from hepatic damage .