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Association of polymorphisms in human leukocyte antigen class I and transporter associated with antigen processing genes with resistance to human immunodeficiency virus type 1 infection

  1. Author:
    Liu, C. L.
    Carrington, M.
    Kaslow, R. A.
    Gao, X. J.
    Rinaldo, C. R.
    Jacobson, L. P.
    Margolick, J. B.
    Phair, J.
    O'Brien, S. J.
    Detels, R.

  2. Author Address

    Univ Calif Los Angeles, Dept Epidemiol, Sch Publ Hlth, Box 951772, Los Angeles, CA 90095 USA Univ Calif Los Angeles, Dept Epidemiol, Sch Publ Hlth, Los Angeles, CA 90095 USA SAIC, Basic Res Program, Frederick, MD USA NCI, Lab Genom Divers, Frederick, MD 21701 USA Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA Northwestern Univ, Howard Brown Hlth Ctr, Chicago, IL 60611 USA Detels R Univ Calif Los Angeles, Dept Epidemiol, Sch Publ Hlth, Box 951772, Los Angeles, CA 90095 USA
    1. Year: 2003
  2. Journal: Journal of Infectious Diseases
    1. 187
    2. 9
    3. Pages: 1404-1410
  4. Type of Article: Article
  1. Abstract:

    To examine the relationship of human leukocyte antigen (HLA) class I and transporter associated with antigen processing (TAP) genes with resistance to human immunodeficiency virus type 1 (HIV-1) infection, 100 HIV-seronegative men who had been exposed repeatedly to HIV-1 were compared with 184 men who had seroconverted to HIV positive and had lower risk. In the univariate analysis, the HLA-A2 supertype, excluding A*0201 (HLA-A2/6802 supertype; odds ratio [OR], 4.45; 95% confidence interval [CI], 1.33-4.84; P = .009) was associated with resistance to HIV-1 infection; the effect was the result of the presence of the A*0205 subgroup alleles. Susceptibility was associated in univariate analysis with the B*35 Px alleles (OR, 0.29; 95% CI, 0.08-0.99; P = .037), which suggests that differential preferences for amino acids at the C terminus may influence peptide-binding capacity. TAP2 Ala665 was also associated with resistance (OR, 2.26; 95% CI, 1.35-3.79; P = . 002), perhaps because of its higher efficiency in transporting peptides, thus eliciting a greater CD8(+) T cell response, or because of linkage disequilibrium. In multivariate logistic analysis, only the A*0205 subgroup (OR, 5.56; 95% CI, 1.34- 23.10; P = .018) and the TAP2 Ala665 (OR, 2.22; 95% CI, 1.28- 3.84; P = .005) were associated with resistance.

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