Genetic Susceptibility Study Of Immune Response To Hepatitis B Vaccination

BackgroundsInfection of hepatitis B virus (HBV) is a worldwide public health problem. It is estimated that there are350million carriers of HBV all over the world, including approximately100million Chinese patients. Hepatitis B vaccination is the dominant and effective method to prevent infection and transmission of HBV. However, there are still about1-10%of recipients failing to elicit protective levels of antibody against the recombinant hepatitis B vaccines (anti-HBs). Butyrophin-like2(BTNL2), a member of butyrophin-like family, is genetic homology to B7costimulatory molecules and plays significant roles in the processes of immune regulation and regulatory T cell (Treg) development. However, its relationship with the immune response to hepatitis B vaccination has yet to be appreciated. The aim of the study was to investigate the association between the polymorphisms of the BTNL2gene and the immune response to hepatitis B vaccination in a Chinese Han population.MethodsA total of1606individuals were recruited in the study, including1040high response subjects (anti-HBs≥1,000mIU/ml) and566no response subjects (anti-HBs<10mIU/ml). A total of7single nucleotide polymorphisms (SNPs) in the nearGene-5region and exon region of the BTNL2gene were analyzed by TaqMan-MGB or TaqMan-HBQ Probe-based Real-time Polymerase Chain Reaction in566non-responders and1040high-responders to hepatitis B vaccination. ResultsIn the study, immunoblotting showed that BTNL2protein was upregulated by recombinant hepatitis B vaccine in THP-1cells. All SNPs genotyped in the study showed significant association with the immune response to hepatitis B vaccination. The frequencies of the minor alleles T, T, C, A, G of rs3763316, rs3763311, rs9268494, rs3806156and rs2076530were significantly higher in the non-responders than in the high-responders (P=2.00e-07, OR=1.58; P=0.002, OR=1.27;P=2.90e-06, OR=1.41; P=0.015, OR=1.20;P＝0.029, OR=1.18; respectively). The frequencies of the minor alleles T, C of rs9268501and rs3763313were significantly higher in the high-responders than in the non-responders (P=0.007, OR=0.81; P=0.004, OR=0.74). Heplotype analysis revealed that the risks of no response to hepatitis B vaccination were increased significantly among individuals harbored the haplotypes of G-T-A-T-C-A-G (P=0.038, adjusted OR-1.48and95%CI=1.02-2.15), G-T-A-T-C (P<0.0001, adjusted OR=2.34and95%CI=1.64-3.33), A-A (P<0.0001, adjusted OR=4.08and95%CI=3.12-5.33) and C-G (P<0.0001, adjusted OR=4.75and95%CI=3.54-6.36) compared with those carried the T-C-A-C-A-C-A, T-C-A-C-A and C-A haplotypes. However, the haplotype of G-C-A-T-C (P=1.00e-04, adjusted OR=0.54and95%CI=0.40-0.76) was a protective construction of the immune response to hepatitis B vaccination compared with the T-C-A-C-A haplotype in the study.ConclusionsThis study reveals that genetic variants in the BTNL2gene are associated strongly with the immune response to hepatitis B vaccination in a Chinese Han population. Considering the negative immune regulation of the BTNL2protein, the findings suggest that the BTNL2protein may affect the outcome of the immune response to hepatitis B vaccination.