Copy Number Variants In FCGR3A And FCGR3B Gene Can Impact The Outcome Of Hepatitis B Virus Infection

ObjectiveCopy number variants are common features of the human genome that play an important role in evolution,contribute to population diversity,development of certain diseases,and influence host emicrobiome interactions.CNVs include more total nucleotides and arise more frequently than single nucleotide polymorphisms,and they are increasingly recognized as an important source of quantitative genetic variation.We investigate the correlation between copy number variations（CNVs）of FCGR3A（Fc gamma receptors 3A）and FCGR3B（Fc gamma receptors 3B）genes and different outcome and disease progression after hepatitis B virus（HBV）infection.MethodsPeripheral blood samples from 841 chronic HBV infections and 296 acute self-restricted HBV infections were collected.The chronic HBV infection group was classified into chronic hepatitis B（CHB）,cirrhosis（LC）,and hepatocellular carcinoma（HCC）groups,based on the degree of disease progression.The Accu Copy method was used to quantitatively analyze the FCGR3A and FCGR3B gene CNVs in peripheral blood.The measurement data in accordance with the normal distribution were expressed as（（?）±s）,T test was applicable to comparison between two groups,and analysis of variance was applicable to comparison among groups.The measurement data with abnormal distribution were expressed as median and quartile,and Kruskal-wallis H test was applicable to comparison between multiple groups.Chi-square test was applicable to counting data.The frequency histogram of FCGR3A and FCGR3B gene CN distribution in patients with acute and chronic HBV infection was drawn by graphpad prism 8.0software to compare the difference of CN distribution between the two groups.Age,gender and copy number were taken as independent variables and the outcome of HBV infection（acute/chronic）was taken as dependent variables.The logistic regression model was used to analyze the risk of genetic variant.To study the role of FCGR3 copy number variation in the outcome of chronic HBV infection,and P<0.05 was considered statistically significant.ResultsThe average age of chronic HBV infection group was（44.11±15.87）years.The average age of acute self-restricted HBV infection group was（42.13±15.27）years.There were no significant differences in age（t=1.87,P=0.062）and sex（X~2=2.486,P=0.115）between the two groups.There were significant differences in the CNVs frequency distribution of the chronic HBV infection and acute self-limited HBV infection groups.In the matter of disease progression after chronic HBV infection.There was no significant difference in comparing the CNVs of FCGR3A and FCGR3B between the CHB,LC,and HCC groups（FCGR3A:X2=3.125,P=0.537,FCGR3B:X2=5.274,P=0.260）.All chronic HBV patients were divided into E antigen positive group and E antigen negative group according to the E antigen status in order to compare the difference of FCGR3 gene CNV distribution between two groups.The results showed that FCGR3 gene CNV had no significant difference between the e-antigen positive group and the e-antigen negative group.Reduced or deletion of FCGR3A gene and FCGR3B gene CN was associated with the risk of chronicity of HBV infection[FCGR3A:OR=0.621,95%CI（0.513～0.752）、FCGR3B:OR=0.594,95%CI（0.491～0.719）].ConclusionCN reduction or deletion of the FCGR3A and FCGR3B may be a genetic susceptibility factor for chronicity of HBV infection,but it was not associated with disease progression of chronic viral hepatitis B.