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Psoriasis Patients Are Enriched for Genetic Variants That Protect against HIV-1 Disease

  1. Author:
    Chen, H. Y.
    Hayashi, G.
    Lai, O. Y.
    Dilthey, A.
    Kuebler, P. J.
    Wong, T. V.
    Martin, M. P.
    Vina, M. A. F.
    McVean, G.
    Wabl, M.
    Leslie, K. S.
    Maurer, T.
    Martin, J. N.
    Deeks, S. G.
    Carrington, M.
    Bowcock, A. M.
    Nixon, D. F.
    Liao, W.

  2. Author Address

    [Chen, Haoyan; Hayashi, Genki; Lai, Olivia Y.; Wong, Tami V.; Leslie, Kieron S.; Maurer, Toby; Liao, Wilson] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Dilthey, Alexander; McVean, Gil] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Kuebler, Peter J.; Nixon, Douglas F.] Univ Calif San Francisco, Div Expt Med, San Francisco, CA 94143 USA. [Martin, Maureen P.; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD 21701 USA. [Vina, Marcelo A. Fernandez] Stanford Univ, Dept Pathol, Palo Alto, CA 94304 USA. [Wabl, Matthias] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Deeks, Steven G.] Univ Calif San Francisco, Dept Med, HIV AIDS Program, San Francisco, CA USA. [Bowcock, Anne M.] Washington Univ, Sch Med, Dept Genet, Div Human Genet, St Louis, MO 63110 USA.;Chen, HY (reprint author), Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA;liaowi@derm.ucsf.edu
    1. Year: 2012
    2. Date: Feb
  2. Journal: Plos Genetics
    1. 8
    2. 2
  4. Type of Article: Article
  5. Article Number: e1002514
  6. ISSN: 1553-7390
  1. Abstract:

    An important paradigm in evolutionary genetics is that of a delicate balance between genetic variants that favorably boost host control of infection but which may unfavorably increase susceptibility to autoimmune disease. Here, we investigated whether patients with psoriasis, a common immune-mediated disease of the skin, are enriched for genetic variants that limit the ability of HIV-1 virus to replicate after infection. We analyzed the HLA class I and class II alleles of 1,727 Caucasian psoriasis cases and 3,581 controls and found that psoriasis patients are significantly more likely than controls to have gene variants that are protective against HIV-1 disease. This includes several HLA class I alleles associated with HIV-1 control; amino acid residues at HLA-B positions 67, 70, and 97 that mediate HIV-1 peptide binding; and the deletion polymorphism rs67384697 associated with high surface expression of HLA-C. We also found that the compound genotype KIR3DS1 plus HLA-B Bw4-80I, which respectively encode a natural killer cell activating receptor and its putative ligand, significantly increased psoriasis susceptibility. This compound genotype has also been associated with delay of progression to AIDS. Together, our results suggest that genetic variants that contribute to anti-viral immunity may predispose to the development of psoriasis.

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External Sources

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  2. DOI: 10.1371/journal.pgen.1002514
  3. View record in Web of Science®
  4. WOS: 000300725500032

Library Notes

  1. Fiscal Year: FY2011-2012
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