Association Of IL-10 And IL-10R1 Single Nucleotide Polymorphisms With The Responsiveness To HBV Vaccination In Infants

Hepatitis B virus(HBV)infection is still a serious global public health problem,with 2 billion people infected worldwide,and 240 million of them are chronic HBV infected individuals.In China,there are 93 million people suffering from chronic HBV infection including 20 million HBV patients.It has been reported that people infected with HBV mostly contracted the virus from mother-to-child transmission(MTCT)of HBV.However,epidemiological studies have demonstrated that 5-10% of healthy individuals who received a standard vaccination schedule with hepatitis B vaccines still failed to produce protective levels of antibodies against HBsAg(anti-HBs).Many factors are relevant to immune responses,host genetic factors,as the most important one,has been widely confirmed to be strongly associated with HBV vaccination.Among all the host genetic factors,cytokines play important roles in modulating the immune responses.Interleukin-10(IL-10)is a cytokine recognized for its ability to inhibit antigen-presenting cells(APC)by down-regulating the cell surface expression of HLA molecules,which may affect the immune response.The immune modulating effect of IL-10 starts with its binding to the IL-10 receptor(IL-10R).Gene variants in IL-10 and IL-10R1 will not only influence the expression of these two molecules but also affect the binding ability between IL-10 and its receptor,which may finally affect the immune response.Objective:To investigate the association of IL-10 and IL-10R1 single nucleotide polymorphisms(SNPs)with responsiveness to HBV vaccination in newborns whose mothers were HBsAg(+)/HBeAg(-).Methods:753 infants and their HBsAg(+)/HBeAg(-)mothers who participated in the prevention of MTCT of HBV at the First Hospital of Jilin University from July 2012 to July 2015 were enrolled,40 of them with un-standardized vaccination process,inadequate blood samples,not Han Chinese and failed genotyping were excluded,in total,713 participants were included in the final analysis.All these 713 infants were administered intramuscular injections of 100 IU HBIG and 10μg HepB within 2 hours after birth,followed by administration of 10μg HepB at the ages of 1 month and 6 months.Venous blood samples were collected from infants and detected for HBsAg and anti-HBs at 7 months of age.Four SNPs including rs1800871,rs1800896,rs3021094 and rs3790622 in IL-10 and three SNPs including rs2282494,rs2508450 and rs4252249 in IL-10R1 of Han Chinese infants who didn’t contracted with HBV,followed the standardized vaccination process and with adequate blood samples were sent for genotyping using the MassARRAY technology platform.Anti-HBs and maternal HBV DNA were transformed to their logarithms.Continuous variables were compared by Student’s t-test.Categorical data were compared using χ2 test or Fisher’s exact test when appropriate.The risk factors of low responsiveness to HBV vaccination were calculated using unconditional logistic regression analysis.Covariance analysis was performed to assess the association of genotypes with anti-HBs levels.The haplotype analysis was conducted using SNPStats software.Gene-gene interactions were calculated with the GMDR program.Results:(1)The frequencies of the IL-10 rs3021094 GG genotype,IL-10 rs3790622 GA genotype and A allele were significantly higher in the LR group compared to the HR group(P=0.044,0.049 and 0.027,respectively).(3)The GG genotype of IL-10 rs3021094,the GA+AA genotype of IL-10 rs3790622 and artificial feeding pattern were correlated with a higher risk of low responsiveness to HBV vaccination(OR=3.74,95%CI=1.47-9.49;OR=3.05,95%CI=1.22-7.61;OR=2.75,95%CI=1.09-6.94,respectively).(4)Infants with the GG genotype of IL-10 rs3021094 had lower anti-HBs levels than those with the TT+GT genotype(P=0.029).Infants with artificial feeding pattern had lower anti-HBs levels than those with non-artificial feeding pattern(P<0.001).(5)No haplotype was found to be correlated with responsiveness to HBV vaccination.(6)There was no interaction between IL-10 and IL-10R1 and low responsiveness to HBV vaccination.Conclusions:Our study found that IL-10 gene variants were significantly associated with the immune response to the HBV vaccine.Identifying these infants who born to HBsAg(+)/HBeAg(-)mothers and low responses to hepatitis B vaccination will provide evidence for individualized prevention strategies.