APOBEC3B基因拷贝数变异与HBV感染后不同转归的关系

Association of APOBEC3B copy number variation with the prognosis of hepatitis B virus infection

目的阐明APOBEC3B基因拷贝数在HBV感染后不同转归患者中的分布频率差异及其在临床转归中的作用。方法收集2016年1月-2017年12月于安徽医科大学第一附属医院就诊的296例HBV感染后急性自限性恢复患者和819例不同疾病阶段的慢性HBV感染者外周血标本,慢性HBV感染组中包含慢性乙型肝炎(CHB)患者444例、肝硬化(LC)患者252例和肝细胞癌(HCC)患者123例。采用AccuCopy方法检测两组患者外周血APOBEC3B基因拷贝数,同时收集上述患者的相关临床资料。各组间APOBEC3B拷贝数分布频率比较采用χ2检验。结果在HBV感染后急慢性转归方面,急性自限性恢复组APOBEC3B拷贝数减少和缺失的比例显著低于慢性HBV感染组(46. 96%vs 58. 00%,P=0. 001 1)。在慢性HBV感染后疾病进展方面,随疾病进展,APOBEC3B基因拷贝数缺失的比例在CHB、LC和HCC患者3组间逐渐增加(分别为11. 04%、14. 29%和22. 76%),差异具有统计学意义(χ2=11. 85,P=0. 019)。在慢性HBV感染组中,APOBEC3B拷贝数分布频率在HBeAg阳性组和HBeAg阴性组间差异无统计学意义(χ2=0. 639,P=0. 727)。结论 APOBEC3B基因拷贝数变异与HBV感染后的不同转归密切相关,APOBEC3B基因拷贝数减少和缺失可能是HBV感染慢性化和疾病进展的遗传易感因素。

ObjectiveTo investigate the difference in the distribution frequency of APOBEC3B copy number variations (CNVs) between patients with different outcomes after hepatitis B virus (HBV) infection and the role of APOBEC3B CNVs in clinical outcome. MethodsA total of 296 patients with acute self-limiting recovery after HBV infection and 819 patients with different stages of chronic HBV infection who visited The First Affiliated Hospital of Anhui Medical University from January 2016 to December 2017 were enrolled as acute self limiting recovery group and chronic HBV infection group, respectively, and their peripheral blood samples were collected. Among the 819 patients with chronic HBV injection, 444 had chronic hepatitis B (CHB), 252 had liver cirrhosis (LC), and 123 had hepatocellular carcinoma (HCC). The AccuCopy method was used to measure APOBEC3B CNVs in peripheral blood, and related clinical data were collected for all patients. The chi-square test was used for comparison of distribution frequency of APOBEC3B CNVs between groups. ResultsFor acute or chronic outcome after chronic HBV infection, the acute self limiting recovery group had a significantly lower proportion of patients with reduced or deleted APOBEC3B CNVs than the chronic HBV infection group (46.96% vs 58.00%, P =0.001 1). For disease progression after chronic HBV infection, the HCC group had the highest proportion of patients with deleted APOBEC3B CNVs of 22.76%, followed by the LC group (14.29%) and the CHB group (11.04%), and there was a significant difference between the three groups (χ^2=11.85, P =0.019). In the chronic HBV infection group, there was no significant difference in the distribution frequency of APOBEC3B CNVs between the patients with positive E-antigen and those with negative E-antigen(χ^2=0.639,P=0.727 ). ConclusionAPOBEC3B CNV is associated with the outcome of chronic HBV infection, and reduced and deleted APOBEC3B CNV is a genetic susceptibility factor for chronicity and progression of HBV infection.