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

研究成果査読

18 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号e1002328
ジャーナルPLoS genetics
7
10
DOI
出版ステータスPublished - 10月 2011
外部発表はい

ASJC Scopus subject areas

  • 生態、進化、行動および分類学
  • 分子生物学
  • 遺伝学
  • 遺伝学(臨床)
  • 癌研究

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