Association Study Of Perinatal Factors And Single Nucleotide Polymorphisms From GWAS With Response To Hepatitis B Vaccination In Infants

Objective: To analyze the association of single nucleotide polymorphisms fromGWAS and perinatal environmental factors with poor antibody response to hepatitis Bvaccination in infants.Methods: Case-control design was applied in our research. Excluding positive maternalHBV infection history (55subjects) and infant serological HBsAg examination test (25subjects),370study subjects were selected. HBsAb concentration was examinedquantitatively by using the fluorescent Immunoassay kits (Abbott Laboratories, NorthChicago, IL), and blood clot for extracting DNA, using Axy Prep TM Blood GenomicDNA Minprep kit. Matrix-assisted laser desorption/ionization Time-of-Flight MassSpectrometry was used to perform genotype. Hardy-Weinberg equilibrium was assessedby Chi-square test. Bonferroni correction was applied in multiple tests of statisticalsignificance. The XTGEE program was applied to identify the association of singlenucleotide polymorphisms from GWAS and perinatal environmental factors to poorantibody response of hepatitis B vaccination in infants (anti-HBs<100mIU/ml). TheXTGEE program could adjust for relatedness of subjects within twins’ pairs.Results: Overall,72（19.46%）of370infants had poor responses to HBV vaccine.⑴Lowbirth weight and paternal smoking were associated with an increased risk of poor responseto HBV vaccination（OR=2.55,95%CI:1.33-4.87and OR=4.50,95%CI:2.52-8.03,respectively). Higher Apgar score and gaining more body weight in the1styear of lifereduced this risk.⑵In normal response group, three SNPs (rs9277535、rs3135363andrs17401966) were shown to diverge from Hardy-Weinberg equilibrium（P≤0.031）; in poor response group, two SNPs (rs3077and rs9277535) were shown to diverge fromHardy-Weinberg equilibrium （P≤0.027）.⑶After association analysis of thepolymorphism with poor response to HBV vaccination in infants, allele frequency ofrs9277535（P=0.026）and genotype frequency of rs1414275（P=0.031）were shownstatistical significance in two groups, respectively. However, after Bonferroni correction,there were no longer significant.⑷No significant gene-environment interaction wereshown between polymorphisms (rs1414275and rs9277535) and perinatal environmentalfactors.Conclusion:⑴After three HBV vaccinations, low birth weight, paternal smoking, Apgarscores and weight gain in1styear were associated with poor antibody response to hepatitisB vaccination in infant.⑵After Bonferroni correction, there were no association betweensingle nucleotide polymorphisms from GWAS and poor response to HBV vaccination ininfants.⑶No significant gene-environment interactions were shown betweenpolymorphisms and perinatal environmental factors.