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Current status and prospects of studies on human genetic alleles associated with hepatitis B virus infection


   Chronic hepatitis B virus(HBV)infection can cause a broadspectrum diseases,including from asymptomatic HBV carriersor cryptic hepatitis,to acute hepatitis,chronic hepatitis,Livercirrhosis and primary hepatocellular carcinoma.The variablepattern and clinical outcome of the infection were mainlydetermined by virological itself factors,host immunologicalfactors and genetic factors as well as the experimentalfactors.Among the human genetic factors,major candidateor identified genes involved in the process of HBV infectionfall into the following categories:(1)genes that mediatethe processes of viral entry into hepatocytes,including genesinvolved in viral binding,fusion with cellular membrane andtransportation in target cells;(2)genes that modulate orcontrol the immune response to HBV infection;(3)genesthat participate in the pathological alterations in liver tissue;(4)genes involved in the development of liver cirrhosis andhepatocellular carcinoma associated with chronic HBVinfection,including genes related to mother-to-infanttransmission of HBV infection;and(5)those that contributeto resistance to antiviral therapies.Most of the reports ofhuman genes associated with HBV infection have currentlyfocused on HLA associations.For example,some investigatorsreported the association of the HLA class Ⅱ alleles such asDRB1*1302 or HLA-DRI3 or DQA1*0501-DQB1*0301-DQB1*1102 haplotypes with acute and/or chronic hepatitisB virus infection,respectively.Several pro-inflammatorycytokines such as Th1 cytokines(including IL-2 and IFN-γ)and TNF-α have been identified to participate the processof viral clearance and host immune response to HBV.Incontrast,the Th2 cytokine IL-10 serves as a potent inhibitorof Th1 effector cells in HBV diseases.The MBP polymorphismsin its encoding region were found to be involved in chronicinfection.Thus,reports from various laboratories have shownsome inconsistencies with regard to the effects of hostgenetic factors on HBV clearance and persistence.Sincegenetic interactions are complex,it is unlikely that a singleallelic variant is responsible for HBV resistance orsusceptibility.However,the collective influence of severalsingle nucleotide polymorphisms(SNPs)or haplotype(s)may underlie the natural combinational or synergisticprotection against HBV.The future study including the multi-cohort collaboration will be needed to darify these preliminaryassociations and identify other potential candidate genes.The ongoing study of the distributions and functions of theimplicated allele polymorphisms will not only provide insight into the pathogenesis of HBV infection,but may also providea novel rationale for new methods of diagnosis andtherapeutic strategies.……