title: HLA and cytokine gene polymorphisms are independently associated with responses to hepatitis B vaccination.
abstract: Variable immune responses to hepatitis B virus (HBV) infection and recombinant HBV vaccines have been associated with polymorphisms in several genes within the human leukocyte antigen (HLA) complex. Analyses of polymerase chain reaction (PCR)-based genotyping data from 164 North American adolescents vaccinated with recombinant HBV products confirmed that HLA-DRB1*07 (relative odds [RO] = 5.18, P <.0001) and human immunodeficiency virus type 1 (HIV-1) infection (RO = 3.91, P <.001) were both associated with nonresponse to full-dose vaccination. Further associations were observed with single nucleotide polymorphisms (SNPs) at the IL2 and IL4 loci along with insertion/deletion variants at the IL12B locus (P =.003-.01). Host genetic associations were independent of one another as well as other HLA (A, B, C, and DQB1) and cytokine gene (IL4R, IL6, IL10, and TNF) variants. Statistical adjustments for nongenetic factors (gender, ethnicity, age, HIV-1 infection, and vaccination protocols) did not substantially alter the strengths of the genetic relationships. The overall distribution pattern of genetic variations was similar between the analyzed vaccinees and additional adolescents (n = 292) from the same cohort. In conclusion, DRB1*07 (or a closely linked allele) and immunoregulatory cytokine gene polymorphisms correlate with variable immune response to recombinant HBV vaccines.
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Chengbin
authors.initials: C
authors.lastname: Wang
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Elena
authors.initials: E
authors.lastname: Lobashevsky
authors.forename: Craig M
authors.initials: CM
authors.lastname: Wilson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
mesh_terms: D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics*; D018023:HIV Seronegativity; D015497:HIV-1; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D017325:Hepatitis B Vaccines / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D006579:Heterozygote; D006801:Humans; D016130:Immunophenotyping; D015999:Multivariate Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D016207:Cytokines; D006680:HLA Antigens; D017325:Hepatitis B Vaccines