FCGR3A和FCGR3B基因拷贝数变异对HBV感染转归的影响

Influence of copy number variations in the FCGR3A and FCGR3B genes on the outcome of hepatitis B virus infection

目的探讨FCGR3A和FCGR3B基因拷贝数变异与HBV感染后不同转归和疾病进展的相关性。方法收集2014年1月—2018年12月安徽医科大学第一附属医院和第二附属医院感染病科住院和门诊841例慢性HBV感染者和296例自限性HBV感染者外周血标本,并将慢性HBV感染者根据病情进展程度进一步分为慢性乙型肝炎(CHB)组、肝硬化(LC)组、肝细胞癌(HCC)组。采用AccuCopy技术定量分析两组患者外周血FCGR3A和FCGR3B基因拷贝数变异。计量资料两组间比较采用独立样本t检验,多组间比较采用单因素方差分析和Kruskal-Wallis H检验;计数资料组间比较采用χ^(2)检验。同时采用χ^(2)检验分析FCGR3基因CNV在不同组间的分布差异。应用年龄和性别校正的logistic回归模型综合分析CNV对HBV感染慢性化的影响。结果慢性HBV感染组与自限性HBV感染组的FCGR3A、FCGR3B拷贝数变异频率分布差异均有统计学意义(χ^(2)值分别为11.406、19.143,P值均<0.05)。在慢性HBV感染后疾病进展方面,CHB组、LC组、HCC组间比较FCGR3A、FCGR3B基因拷贝数变异差异无统计学意义(FCGR3A:χ^(2)=3.125,P=0.537,FCGR3B:χ^(2)=5.274,P=0.260)。而且FCGR3A、FCGR3B基因拷贝数变异在HBeAg阳性组和阴性组之间无统计学差异(FCGR3A:χ^(2)=1.025,P=0.599,FCGR3B:χ^(2)=0.712,P=0.701)。FCGR3A基因和FCGR3B基因拷贝数减少或缺失是HBV感染慢性化的危险因素[FCGR3A:OR=0.621,95%CI:0.513~0.752,P<0.001;FCGR3B:OR=0.594,95%CI:0.491~0.719,P<0.001]。结论FCGR3A基因和FCGR3B基因拷贝数减少或缺失可能是HBV感染慢性化的遗传易感因素之一,但与疾病进展无关。

Objective To investigate the association of copy number variations(CNVs)in the FCGR3A and FCGR3B genes with different outcomes and disease progression after hepatitis B virus(HBV)infection.Methods Peripheral blood samples were collected from 841 pa-tients with chronic HBV infection and 296 patients with self-limited HBV infection,an according to the degree of disease progression,the pa-tients with chronic HBV infection were further divided into chronic hepatitis B(CHB)group,liver cirrhosis(LC)group,and hepatocellular carcinoma(HCC)group.The AccuCopy technique was used for the quantitative analysis of CNVs in the FCGR3A and FCGR3B genes in pe-ripheral blood.The independent samples t-test was used for comparison of continuous data between two groups,and a one-way analysis of variance and the Kruskal-Wallis H test were used for comparison between multiple groups;the chi-square test was used for comparison of categorical data between groups.The chi-square test was also used to investigate the difference in the distribution of CNVs in the FCGR3 gene between different groups.The age-and sex-adjusted logistic regression model was used to investigate the influence of CNVs on the chronicity of HBV infection.Results There was a significant difference in the frequency distribution of CNVs in the FCGR3A and FCGR3B genes be-tween the chronic HBV infection group and the self-limited HBV infection group(χ^(2)=11.406 and 19.143,both P<0.05).As for disease progression after chronic HBV infection,there were no significant differences in CNVs of the FCGR3A and FCGR3B genes between the CHB group,the LC group,and the HCC group(FCGR3A:χ^(2)=3.125,P=0.537;FCGR3B:χ^(2)=5.274,P=0.260).There were also no signifi-cant differences in CNVs of the FCGR3A and FCGR3B genes between the HBeAg-positive group and the HBeAg-negative group(FCGR3A:χ^(2)=1.025,P=0.599;FCGR3B:χ^(2)=0.712,P=0.701).Reduction or deletion of the copy number of the FCGR3A and FCGR3B genes was a risk factor for the chronicity of HBV infection(FCGR3A:odds ratio[OR]=0.621,95%confidence interval[CI]:0.513-0.752;FCGR3B:OR=0.594,95%CI:0.491-0.719).Conclusion Reduction or deletion of the copy number of the FCGR3A and FCGR3B genes may be a genetic susceptibility factor for the chronicity of HBV infection,but it is not associated with disease progression.