Relationship Between Cytokine Gene Polymorphism And Susceptibility To HBV Intrauterine Infection

Hepatitis B virus(HBV) is one of the most common microorganismaround the world. There are about 130,000,000-150,000,000 HBV carriersin China, and about half of them are transmitted by mother-infantvertical transmission. Among these HBV carriers by intrauterineinfection, HBV exist persistently within about 90% of them, and thelatter is considered to be in the "immune tolerant" phase. At thesame time, they are usually associated with a very low rate of virologicresponse to anti-virus therapy. Carriers of HBV are also at increasedrisk of developing cirrhosis, hepatic decompensation, andhepatocellular carcinoma(HCC). So interruption of HBV intrauterineinfection is necessary. Hepatitis B immune globulin(HBIG) and concurrent hepatitis Bvaccine have been shown to be 90%-95% efficacious in the prevention ofintrauterine transmission of HBV. However, we still have 5%-10%nonresponders. Immune tolerant after intrauterine infection of HBV is consideredto be occurring in T cell. Scarcity of T cell restricted by MHCⅡantibodyis induced by HBV particles or antigens transmitted through placenta frommother to fetus. The influences of genomic background are confirmed in more and moredisease along with the developing of genomic medicine. Single nucleotidepolymorphisms(SNPs) occupy about 90% of human DNA variation, and areregarded as most important genomic tag. Cytokines work effectively in eliminating virus by immune systemafter HBV infection. Previously we had already investigated cytokinesin children with intrauterine infection of HBV. In this study, we would 4复旦大学博士研究生学位论文investigate relationship between cytokine gene promoter polymorphismand susceptibility to HBV intrauterine infection. Part 1 Relationship between Tumor Necrosis Factor-αpromoter G238A and G308A polymorphism and susceptibility to HBV intrauterine infectionObjective To explore the possible relationship between tumor necrosisfactor(TNF)-α promoter G238A and G308A polymorphism and susceptibilityto HBV intrauterine infection.Methods Two polymorphism sites of TNF-α gene promoter region weredetermined by real-time quantitative fluorescent PCR. (1)TNF-α -238G/Agene polymorphism were determined in 256 children, including 130 infantsborn to HBV-markers positive mothers were divided into two groups: 45children with HBV intrauterine infection(groupⅠ) and 85 childrenwithout HBV intrauterine infection(groupⅡ),and 126 controls. (2)TNF-αpromoter G308A polymorphism were determined in 243 children,including 126 infants born to HBV-markers positive mothers were dividedinto two groups: 35 children with HBV intrauterine infection(groupⅠ)and 91 children without HBV intrauterine infection(groupⅡ),and 117controls.Results (1) No evident difference of TNF-α -238G/A allele frequency wasfound between infants born to HBV-markers positive mothers and thecontrols(x2=2.846,p>0.05);The significant difference of TNF-α -238Aallele frequency was found between groupⅠand groupⅡ(x2=6.797,p=0.009),and between groupⅠand the controls(x2=9.513,p=0.002),butno evident difference between groupⅡand the controls(x2=0.047,p=0.828). (2)No evident difference of TNF-α -308G/A allele frequency wasfound between infants born to HBV-markers positive mothers and thecontrols(x2=0.051,p>0.05),and between groupⅠand groupⅡ(x2=1.361,p>0.05).Conclusion Tumor Necrosis Factor-α promoter G238A polymorphism wasassociated with HBV intrauterine infection. There was no evidentrelationship between Tumor Necrosis Factor-α promoter G308Apolymorphism and susceptibility to HBV intrauterine infection. 5复旦大学博士研究生学位论文 Part 2 Relationship between Tumor Necrosis Factor-α promoter G238A polymorphism and gene expressionObjective To explore if Tumor Necrosis Facto...