HLA and cytokine gene polymorphisms are independently associated with responses to hepatitis B vaccination

Authors

  • Chengbin Wang,

    1. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama
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  • Jianming Tang,

    Corresponding author
    1. Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
    • Program in Epidemiology of Infection and Immunity, School of Public Health, University of Alabama at Birmingham, 1665 University Blvd., Birmingham, AL 35294-0022
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    • fax: 205-934-8665

  • Wei Song,

    1. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama
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  • Elena Lobashevsky,

    1. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama
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  • Craig M. Wilson,

    1. Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
    2. Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
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  • Richard A. Kaslow

    Corresponding author
    1. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama
    2. Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
    • Program in Epidemiology of Infection and Immunity, School of Public Health, University of Alabama at Birmingham, 1665 University Blvd., Birmingham, AL 35294-0022
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    • fax: 205-934-8665


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. (HEPATOLOGY 2004;39:978–988.)

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