Document Detail


CCR5 promoter polymorphisms, CCR5 59029A and CCR5 59353C, are under represented in HIV-1-infected long-term non-progressors. The Australian Long-Term Non-Progressor Study Group.
MedLine Citation:
PMID:  10708279     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To determine the influence of CCR5 promoter polymorphisms on HIV-1 progression to AIDS and to evaluate the interaction between CCR5 structural polymorphisms and those occurring in the regulatory region of the same gene. PARTICIPANTS: Seventy-one HIV-1-infected long-term non-progressors with a CD4+ T cell count of > 500 x 10(6)/I more than 8 years after infection were compared with 75 HIV-1-infected individuals who had progressed to AIDS and/or death within 8 years and with a further 119 HIV-1-positive patients who had CD4+ T cell counts of 200-500 x 10(6)/l. An additional 92 HIV-negative individuals were also studied. METHODS: CCR5 delta32 genotype was determined by PCR with primers spanning the 32 base pair deletion. CCR2-64I, CCR5 59029A/G and CCR5 59353C/T genotypes were determined by PCR followed by restriction fragment length polymorphism analysis. RESULTS: Strong linkage disequilibrium between the CCR5 59029A and CCR5 59353C polymorphic variants was identified. CCR5 59029A and CCR5 59353C homozygotes were found to be significantly under-represented in the long-term non-progressor group as compared with the other HIV-1-positive groups, with the effect being more marked in the absence of the CCR5 delta32 and CCR2 64I mutations. CONCLUSIONS: This study provides the first evidence for an association between CCR5 promoter polymorphisms and long-term asymptomatic HIV-1 infection, with individuals lacking the CCR5 59029A/CCR5 59353C homozygous genotype likely to progress more slowly towards AIDS and/or death.
Authors:
A O Clegg; L J Ashton; R A Biti; P Badhwar; P Williamson; J M Kaldor; G J Stewart
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  AIDS (London, England)     Volume:  14     ISSN:  0269-9370     ISO Abbreviation:  AIDS     Publication Date:  2000 Jan 
Date Detail:
Created Date:  2000-04-20     Completed Date:  2000-04-20     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  103-8     Citation Subset:  IM; X    
Affiliation:
Department of Immunology, Westmead Hospital, University of Sydney, Australia.
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MeSH Terms
Descriptor/Qualifier:
Acquired Immunodeficiency Syndrome / genetics*
Genotype
HIV Long-Term Survivors
HIV-1*
Heterozygote
Homozygote
Humans
Mutation
Polymerase Chain Reaction
Polymorphism, Genetic
Polymorphism, Restriction Fragment Length
Promoter Regions, Genetic
Prospective Studies
Receptors, CCR2
Receptors, CCR5 / genetics*
Receptors, Chemokine*
Receptors, Cytokine / genetics
Chemical
Reg. No./Substance:
0/CCR2 protein, human; 0/Receptors, CCR2; 0/Receptors, CCR5; 0/Receptors, Chemokine; 0/Receptors, Cytokine

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