| Objective: To study the influencing factors of mother-to-child transmission of hepatitis B virus(HBV) and the immunoprophylaxis efficacy. Analyze the association between HLA-DP/DQ genetic variants and HBV infection in children, so as to provide scientific evidence for HBV control.Methods:(1) The study subjects were consecutively recruited among Children’s Hospital and the First Affiliated Hospital of Chongqing Medical University、Maternal and Child Health Hospital of Chongqing Yuzhong District 、Chengdu Women & Children’s Central Hospital from October 2013 to August 2013. Retrospective survey by questionaires was conducted among HBs Ag(+) mothers deliverying during April, 2011 and August, 2014 in two tertiary hospitals in Chongqing and Chengdu along with their children exposed to HBV. The history diseases of mothers, delivery modes, feeding patterns and immunization of children were investigated. Blood samples of these children were collected. Enzyme-linked immune sorbent assay(ELISA) reagents was used to test the serological markers of HBV. Children who had detected HBs Ag(+) were selected as cases. The rest were matched as control. 1:4 matched case control study and conditional logistic regression was adopted to analyze the influencing factors of mother-to-child transmission of HBV.(2) The research objects were children who successfully collected blood samples in the above three hospitals in Chongqing. Human genomic DNA samples were extracted from venous blood samples. Seven SNPs at HLA-DP and HLA-DQ loci were selected as the research subjects. SNP genotypes were test by the Sequenom Mass Array. Binary logistic regression was adopted to analyze the association with HBV infection in children. Haplotype-based association analysis was used by Phase2.0 software. The interaction of these SNPs was analyzed by MDR3.0.2 and GMDR0.7 software.Results:(1) Hepatitis B vaccine coverage rate among children at high risk of HBV was 100% and 96.55% of them received combined injection of hepatitis B vaccine and hepatitis B immunoglobulin(HBIG). HBs Ag positive rate was 3.09%,no significant difference caused by age discrepancy. HBs Ab positive rate was 69.15%, decreasing with the increase of age(x~2=28.135,P<0.001). HBs Ag and HBs Ab positive rates between different sexes had no significant difference.(2) Infection rate of children with HBs Ag and HBe Ag double positive mothers was 15.09%, higher than those in HBs Ag positive group(0.22%), P< 0.01. Mothers of HBe Ag positive was a important risk factor of mother-to-child transmission of HBV in these children(OR=33.534,95%CI: 4.365-257.596).(3) The results of univariate analysis showed that the genotype frequency distribution of HLA-DPA1 rs3077 and HLA-DPB1 rs9277535 had significant difference in the case group and the control group(P<0.05). Compared with A allele, G allele of rs3077 and rs9277535 had a higher risk of HBV infection in children(OR=1.309, 95%CI: 1.046-1.639; OR=1.411, 95%CI: 1.125-1.771). After adjusted children’s sex and age and whether mothers of HBV infected, rs9366816 TC genotype significantly increased the risk of HBV infection, as compared with TT genotype(OR=1.789, 95% CI: 1.118-2.863). In addition, by using genetic model analysis, rs2281388 GA genotype was also found a higher risk of HBV infection, as compared with GG+AA genotype(OR=1.430, 95%CI: 1.041-1.966).(4) The results of univariate analysis showed that the GA genotype frequency distribution of rs3077 and rs9277535 had significant difference in the HBV breakthrough infection children and the controls(P < 0.05). Compared with A allele, G allele of rs9277535 had a higher risk of HBV breakthrough infection(OR=1.510, 95% CI: 1.029-2.215). By using genetic model analysis, compared with GA+AA genotype, rs9277535 GG genotype significantly increased the risk of HBV breakthrough infection in children(OR=2.031, 95%CI: 1.167-3.534). While, GA genotype significantly decreased the risk of HBV breakthrough infection(OR=0.050, 95%CI: 0.006-0.392), as compared with GG genotype.Conclusion:(1) HBs Ab positive rate among children at high risk of HBV is low and decreasing with the increase of age.(2) The maternal HBe Ag positive is the main risk factor for mother-to-child transmission of HBV, and it may lead to non-response to hepatitis B vaccine.(3) rs3077、rs9277535、rs2281388 and rs9366816 located in HLA-DP is related with HBV infection in children.(4) rs9277535 located in HLA-DPB1 is associated with HBV breakthrough infection in children born of HBs Ag positive mothers. |
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