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Role of exonic variation in chemokine receptor genes on AIDS: CCRL2 F167Y association with pneumocystis pneumonia
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نویسنده
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an p. ,li r. ,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.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 10
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چکیده
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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.
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آدرس
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basic research laboratory,saic-frederick,national cancer institute-frederick,frederick,md, United States, office of population genomics,national human genome research institute,bethesda,md, United States, laboratory of molecular immunoregulation,national cancer institute-frederick,frederick,md, United States, laboratory of molecular immunoregulation,national cancer institute-frederick,frederick,md, United States, laboratory of molecular immunoregulation,national cancer institute-frederick,frederick,md, United States, department of microbiology,university of washington school of medicine,seattle,wa, United States, laboratory of genomic diversity,national cancer institute-frederick,frederick,md, United States, division of infectious diseases,feinberg school of medicine,northwestern university medical school,chicago,il, United States, infections and immunoepidemiology branch,national cancer institute,bethesda,md, United States, department of epidemiology,johns hopkins bloomberg school of public health,baltimore,md, United States, bsp/ccr genetics core,saic-frederick,national cancer institute-frederick,frederick,md, United States, laboratory of genomic diversity,national cancer institute-frederick,frederick,md, United States, san francisco department of public health,san francisco,ca, United States, rho,chapel hill,nc, United States, bsp/ccr genetics core,saic-frederick,national cancer institute-frederick,frederick,md, United States, basic research laboratory,saic-frederick,national cancer institute-frederick,frederick,md, United States
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Authors
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