Association Of Polymorphisms Of FAS (-1377G�'A�'�-670A�'G),FASL (-844C�'T)及CASP8 (-652 6N Ins�'del) Gene With Outcomes Of Hepatitis B Virus Infection In Han Population Of North China

The clinical outcomes of hepatitis B virus(HBV) infection are extremely variable, and might be associated with genetic differences of the host.It is suggested that that T-cell responses,especially the responses of cytotoxic T lymphocytes(CTLs),play a central role in viral clearance.CTLs kill cells through perforin and Fas/Fas ligand (FasL)-mediated death pathways.The polymorphisms of apoptosis pathway genes might be associated with the outcomes of HBV infection.Methods:Genotypes were determined in 207 chronic HB patients,203 chronic inactive HBV carriers and 150 spontaneous recovery subjects by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Odds ratios(OR) and 95%confidence intervals(95%CI) were estimated by logistic regression,and all statistical tests were two sided.Results:1.The frequency of CASPS-652 6N del/del genotype in inactive HBV carriers was significantly higher than that in chronic HB.HBV carriers having CASP8-652 6N del/del genotype had an OR of 0.03(95%CI:0.01-0.06) for developing Chronic HB comparing with subjects having CASP8-652 6N ins/ins genotype.The frequencies of CASPS-652 6N ins/del and CASP8-652 6N del/del genotypes in spontaneous recovery subjects were significantly higher than those in chronic HB.Spontaneous recovery subjects having CASPS-652 6N ins/del and CASPS-652 6N del/del genotype had an OR of 0.22(95%CI: 0.09-0.52) or 0.02(95%CI:0.01-0.04),respectively,for developing Chronic HB comparing with subjects having CASPS-652 6N ins/ins genotype.2.The frequency of FAS-1377GG genotype in Chronic HB combined with inactive HBV carriers was significantly higher that in spontaneous recovery subjects. Spontaneous recovery subjects having FAS-1377GG genotype had an OR of 0.58(95%CI: 0.35-0.94) for developing chronic HB and chronic inactive HB carriers comparing with subjects having FAS-1377AA or GA genotypes.3.No gene-gene interaction between the FAS-1377 and CASP8-652 variants were detected in reducing the risk of chronic HB.4.A multiplicative joint effect between the CASP8-652 6N del/del genotype and smoking or drinking in intensifying risk of chronic HB was also evident.Conclusions:These results suggest that genetic variations in the death pathway genes FAS and CASP8 are involved in different clinical outcomes of HBV infection.