Role of exonic variation in chemokine receptor genes on AIDS: CCRL2 F167Y association with pneumocystis pneumonia

Ping An, Rongling Li, Ji Ming Wang, Teizo Yoshimura, Munehisa Takahashi, Ram Samudralal, Stephen J. O'Brien, John Phair, James J. Goedert, Gregory D. Kirk, Jennifer L. Troyer, Efe Sezgin, Susan P. Buchbinder, Sharyne Donfield, George W. Nelson, Cheryl A. Winkler

Research output: Contribution to journalArticle

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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-naïve 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.

Original languageEnglish
Article numbere1002328
JournalPLoS Genetics
Volume7
Issue number10
DOIs
Publication statusPublished - Oct 2011
Externally publishedYes

Fingerprint

Pneumocystis
Pneumocystis Pneumonia
pneumonia
Chemokine Receptors
acquired immune deficiency syndrome
Acquired Immunodeficiency Syndrome
Human immunodeficiency virus 1
human immunodeficiency virus
gene
HIV-1
single nucleotide polymorphism
Genes
genes
Single Nucleotide Polymorphism
polymorphism
dendritic cells
Chromosomes, Human, Pair 22
trafficking
natural history
disease course

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Role of exonic variation in chemokine receptor genes on AIDS : CCRL2 F167Y association with pneumocystis pneumonia. / An, Ping; Li, Rongling; Wang, Ji Ming; Yoshimura, Teizo; Takahashi, Munehisa; Samudralal, Ram; O'Brien, Stephen J.; Phair, John; Goedert, James J.; Kirk, Gregory D.; Troyer, Jennifer L.; Sezgin, Efe; Buchbinder, Susan P.; Donfield, Sharyne; Nelson, George W.; Winkler, Cheryl A.

In: PLoS Genetics, Vol. 7, No. 10, e1002328, 10.2011.

Research output: Contribution to journalArticle

An, P, Li, R, Wang, JM, Yoshimura, T, Takahashi, M, Samudralal, R, O'Brien, SJ, Phair, J, Goedert, JJ, Kirk, GD, Troyer, JL, Sezgin, E, Buchbinder, SP, Donfield, S, Nelson, GW & Winkler, CA 2011, 'Role of exonic variation in chemokine receptor genes on AIDS: CCRL2 F167Y association with pneumocystis pneumonia', PLoS Genetics, vol. 7, no. 10, e1002328. https://doi.org/10.1371/journal.pgen.1002328
An, Ping ; Li, Rongling ; Wang, Ji Ming ; Yoshimura, Teizo ; Takahashi, Munehisa ; Samudralal, Ram ; O'Brien, Stephen J. ; Phair, John ; Goedert, James J. ; Kirk, Gregory D. ; Troyer, Jennifer L. ; Sezgin, Efe ; Buchbinder, Susan P. ; Donfield, Sharyne ; Nelson, George W. ; Winkler, Cheryl A. / Role of exonic variation in chemokine receptor genes on AIDS : CCRL2 F167Y association with pneumocystis pneumonia. In: PLoS Genetics. 2011 ; Vol. 7, No. 10.
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