The Effect Of ICOS Polymorphisms Interaction With HBV Viral Mutations On The Outcomes Of HBV Subtypes Infection

Background: Hepatitis B virus(HBV)infection remains a significant public health problem in the world,particularly in Chinese Han population.Polymorphisms of inducible costimulator(ICOS)have been confirmed involving in chronic HBV infection in our previous research.The results of HBV infection are influenced by various virological,immunological,and host genetic factors.Meanwhile,HBV mutations impact the outcomes of HBV infection has been verified in past studies.The purpose of this study is to explore the effect of ICOS single nucleotide polymorphisms in different HBV subtypes and their interactions with viral mutations on the outcomes of HBV infection.Methods: A total of 1,636 Chinese Han individuals were recruited,including 47 asymptomatic HBV carriers(ASC),353 chronic hepatitis B patients(CHB),327 HBV-related liver cirrhosis patients(LC),193 patients with HBV-related hepatocellular carcinoma(HCC),464 patients with spontaneous recovery from HBV infection(SR),and 252 healthy controls(HC).DNA samples from these subjects were genotyped for four ICOS SNPs(rs11883722,rs10932029,rs1559931,and rs4675379)us ing Taq Man SNP Genotyping Assay and analyzed.Direct sequencing was used to determine the HBV mutations in enhancer II region/ basal core promoter region/precore region.Associations of polymorphisms and HBV mutations were evaluated by binary logistic regression adjusted for age and sex.Results: We found that ICOS rs10932029 SNP(TC vs.TT)was associated with decreased HBV-related LC risk in genotype C(P = 0.003,OR= 0.261).The mutations of A1762T(P = 0.000,OR= 4.784),G1764A(P = 0.019,OR= 4.035)and A1762T/G1764A(P = 0.000,OR= 9.133)had increased risk of LC in genotype C.The further study indicated that interactions of ICOS rs10932029(TC vs.TT)with A1762T(P = 0.014,OR = 0.144)or A1762T/G1764A(P = 0.014,OR = 0.123)mutations significantly decreased liver cirrhosis(LC)risk only in genotype C.However,interaction of ICOS rs10932029(TC vs.TT)with G1764 A mutation has no significantly association with LC.Conclusion: Rs10932029 genotype “TC” might be a LC-protective factor in HBV genotype C infection.The interactions between rs10932029 genotype “TC” with A1762 T or A1762T/G1764 A mutation could decrease the risk of LC.