Skip NavigationSkip to Content
Return Return to Search Results

Role of Exonic Variation in Chemokine Receptor Genes on AIDS: CCRL2 F167Y Association with Pneumocystis Pneumonia

  1. Author:
    An, P.
    Li, R. L.
    Wang, J. M.
    Yoshimura, T.
    Takahashi, M.
    Samudralal, R.
    O'Brien, S. J.
    Phair, J.
    Goedert, J. J.
    Kirk, G. D.
    Troyer, J. L.
    Sezgin, E.
    Buchbinder, S. P.
    Donfield, S.
    Nelson, G. W.
    Winkler, C. A.

  2. Author Address

    [An, P; Winkler, CA] NCI, Basic Res Lab, SAIC Frederick, Frederick, MD 21701 USA. [Li, RL] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA. [Wang, JM; Yoshimura, T; Takahashi, M] NCI, Mol Immunoregulat Lab, Frederick, MD 21701 USA. [Samudralal, R] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. [O'Brien, SJ; Sezgin, E] NCI, Lab Genom Divers, Frederick, MD 21701 USA. [Phair, J] Northwestern Univ, Div Infect Dis, Feinberg Sch Med, Sch Med, Chicago, IL USA. [Goedert, JJ] NCI, Infect & Immunoepidemiol Branch, Bethesda, MD 20892 USA. [Kirk, GD] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Troyer, JL; Nelson, GW] NCI, BSP CCR Genet Core, SAIC Frederick, Frederick, MD 21701 USA. [Buchbinder, SP] San Francisco Dept Publ Hlth, San Francisco, CA USA. [Donfield, S] Rho, Chapel Hill, NC USA.;An, P (reprint author), NCI, Basic Res Lab, SAIC Frederick, Frederick, MD 21701 USA;pingan@nih.gov winklerc@mail.nih.gov
    1. Year: 2011
    2. Date: Oct
  2. Journal: Plos Genetics
    1. 7
    2. 10
    3. Pages: 10
  4. Type of Article: Article
  5. Article Number: e1002328
  6. ISSN: 1553-7390
  1. Abstract:

    Chromosome 3p21-22 harbors two clusters of chemokine receptor genes, several of which serve as major or minor coreceptors of HIV-1. Although the genetic association of CCR5 and CCR2 variants with HIV-1 pathogenesis is well known, the role of variation in other nearby chemokine receptor genes remain unresolved. We genotyped exonic single nucleotide polymorphisms (SNPs) in chemokine receptor genes: CCR3, CCRL2, and CXCR6 (at 3p21) and CCR8 and CX3CR1 (at 3p22), the majority of which were non-synonymous. The individual SNPs were tested for their effects on disease progression and outcomes in five treatment-naive HIV-1/AIDS natural history cohorts. In addition to the known CCR5 and CCR2 associations, significant associations were identified for CCR3, CCR8, and CCRL2 on progression to AIDS. A multivariate survival analysis pointed to a previously undetected association of a non-conservative amino acid change F167Y in CCRL2 with AIDS progression: 167F is associated with accelerated progression to AIDS (RH = 1.90, P = 0.002, corrected). Further analysis indicated that CCRL2-167F was specifically associated with more rapid development of pneumocystis pneumonia (PCP) (RH = 2.84, 95% CI 1.28-6.31) among four major AIDS-defining conditions. Considering the newly defined role of CCRL2 in lung dendritic cell trafficking, this atypical chemokine receptor may affect PCP through immune regulation and inducing inflammation.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1371/journal.pgen.1002328
  3. View record in Web of Science®
  4. WOS: 000296665400029

Library Notes

  1. Fiscal Year: FY2011-2012
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel