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Genome-wide Association Study Implicates PARD3B-based AIDS Restriction

  1. Author:
    Troyer, J. L.
    Nelson, G. W.
    Lautenberger, J. A.
    Chinn, L.
    McIntosh, C.
    Johnson, R. C.
    Sezgin, E.
    Kessing, B.
    Malasky, M.
    Hendrickson, S. L.
    Li, G.
    Pontius, J.
    Tang, M. Z.
    An, P.
    Winkler, C. A.
    Limou, S.
    Le Clerc, S.
    Delaneau, O.
    Zagury, J. F.
    Schuitemaker, H.
    van Manen, D.
    Bream, J. H.
    Gomperts, E. D.
    Buchbinder, S.
    Goedert, J. J.
    Kirk, G. D.
    O'Brien, S. J.

  2. Author Address

    [Troyer, JL; Nelson, GW; Johnson, RC; Kessing, B; Malasky, M; Li, G; Pontius, J; An, P; Winkler, CA] NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA [Limou, S; Le Clerc, S; Delaneau, O; Zagury, JF] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA [Schuitemaker, H; van Manen, D] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA [Bream, JH] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA [Gomperts, ED] Childrens Hosp Los Angeles, Dept Hematol, Los Angeles, CA USA [Buchbinder, S] San Francisco Dept Publ Hlth, HIV Res Sect, San Francisco, CA USA [Goedert, JJ] Conservatoire Natl Arts & Metiers, Chaire Bioinformat, Paris, France [Kirk, GD] Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, Landsteiner Lab, NL-1012 WX Amsterdam, Netherlands [Kirk, GD] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam CINIMA, NL-1012 WX Amsterdam, Netherlands;Troyer, JL (reprint author), NCI, Lab Genom Divers, SAIC Frederick Inc, Bldg 560,Rm 21-56, Frederick, MD 21702 USA;troyerj@mail.nih.gov
    1. Year: 2011
    2. Date: May
  2. Journal: Journal of Infectious Diseases
    1. 203
    2. 10
    3. Pages: 1491-1502
  4. Type of Article: Article
  5. ISSN: 1537-6613
  1. Abstract:

    Methods. European American HIV seroconverters (n = 755) were interrogated for single-nucleotide polymorphisms (SNPs) (n = 700,022) associated with progression to AIDS 1987 (Cox proportional hazards regression analysis, co-dominant model). Results. Association with slower progression was observed for SNPs in the gene PARD3B. One of these, rs11884476, reached genome-wide significance (relative hazard = 0.3; P =3. 370 x 10(-9)) after statistical correction for 700,022 SNPs and contributes 4.52% of the overall variance in AIDS progression in this study. Nine of the top-ranked SNPs define a PARD3B haplotype that also displays significant association with progression to AIDS (hazard ratio, 0.3; P = 3.220 x 10(-8)). One of these SNPs, rs10185378, is a predicted exonic splicing enhancer; significant alteration in the expression profile of PARD3B splicing transcripts was observed in B cell lines with alternate rs10185378 genotypes. This SNP was typed in European cohorts of rapid progressors and was found to be protective for AIDS 1993 definition (odds ratio, 0.43, P = .025). Conclusions. These observations suggest a potential unsuspected pathway of host genetic influence on the dynamics of AIDS progression.

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External Sources

  1. View Full Text
  2. DOI: 10.1093/infdis/jir046
  3. View record in Web of Science®
  4. WOS: 000289838800018

Library Notes

  1. Fiscal Year: FY2010-2011
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