Allelic variants of human beta-chemokine receptor 5 (CCR5) promoter: Evolutionary relationships and predictable associations with HIV-1 disease progression

J. Tang, C. Rivers, E. Karita, C. Costello, S. Allen, P. N. Fultz, Ellie Schoenbaum, R. A. Kaslow

Research output: Contribution to journalArticle

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Abstract

Variability in the natural history of HIV-1 infection has been repeatedly associated with genetic variants in the beta-chemokine receptor 5 (CCR5) locus. While CCR5 coding sequences have demonstrated relatively limited variation, sequences of its promoter appear polymorphic in all major populations. Our studies revealed five major CCR5 promoter alleles with distributions that differed widely among the four distinct ethnic groups from Kigali, Rwanda and Bronx, New York. In particular, promoter allele P*0103 (G59029-T59353-T59356-A59402-C 59653) was largely restricted to black subjects. The promoter allele P*0202 (A59029-C59353-C59356-A59402-T 59653) was tightly linked to the slightly less frequent CCR2b-641, a variant of the CCR2b gene, which is about 12.7 kbp upstream from the promoter region. Another closely related promoter allele P*0201 (A59029-C59353-C59356-A59402-C 59653) exclusively carried the far less common CCR5-Δ32, a 32-bp deletion in the CCR5 coding sequence 2 kbp downstream from the promoter. The homozygous P*0201/*0201 genotype can be predicted as a risk factor for more rapid disease progression. Among human, chimpanzee, pig-tailed macaque, and sooty mangabey promoter allelic sequences, the apparent ancestral lineage of the promoter sequence (G59029-T59353-C59356-A59402-C 59653 = human P*0102) was highly conserved across the primate species analyzed here while P*0201 and P*0202 arose more recently than the other three major alleles. Further effort to establish the mechanism by which CCR chemokine receptor polymorphisms govern the initiation and pathogenesis of primate lentivirus infection apparently requires fully detailed genotypic characterization of the affected populations.

Original languageEnglish (US)
Pages (from-to)20-27
Number of pages8
JournalGenes and Immunity
Volume1
Issue number1
StatePublished - Sep 1999

Fingerprint

CC Chemokines
Chemokine Receptors
Disease Progression
HIV-1
Alleles
Cercocebus atys
Lentivirus Infections
CCR Receptors
Primate Lentiviruses
Rwanda
Pan troglodytes
Macaca
Ethnic Groups
Genetic Promoter Regions
Primates
Population
HIV Infections
Swine
Genotype
Genes

Keywords

  • AIDS
  • CCR2b
  • CCR5
  • CCR5 promoter
  • Genetic variation
  • HIV-1

ASJC Scopus subject areas

  • Genetics
  • Immunology
  • Genetics(clinical)

Cite this

Tang, J., Rivers, C., Karita, E., Costello, C., Allen, S., Fultz, P. N., ... Kaslow, R. A. (1999). Allelic variants of human beta-chemokine receptor 5 (CCR5) promoter: Evolutionary relationships and predictable associations with HIV-1 disease progression. Genes and Immunity, 1(1), 20-27.

Allelic variants of human beta-chemokine receptor 5 (CCR5) promoter : Evolutionary relationships and predictable associations with HIV-1 disease progression. / Tang, J.; Rivers, C.; Karita, E.; Costello, C.; Allen, S.; Fultz, P. N.; Schoenbaum, Ellie; Kaslow, R. A.

In: Genes and Immunity, Vol. 1, No. 1, 09.1999, p. 20-27.

Research output: Contribution to journalArticle

Tang, J. ; Rivers, C. ; Karita, E. ; Costello, C. ; Allen, S. ; Fultz, P. N. ; Schoenbaum, Ellie ; Kaslow, R. A. / Allelic variants of human beta-chemokine receptor 5 (CCR5) promoter : Evolutionary relationships and predictable associations with HIV-1 disease progression. In: Genes and Immunity. 1999 ; Vol. 1, No. 1. pp. 20-27.
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abstract = "Variability in the natural history of HIV-1 infection has been repeatedly associated with genetic variants in the beta-chemokine receptor 5 (CCR5) locus. While CCR5 coding sequences have demonstrated relatively limited variation, sequences of its promoter appear polymorphic in all major populations. Our studies revealed five major CCR5 promoter alleles with distributions that differed widely among the four distinct ethnic groups from Kigali, Rwanda and Bronx, New York. In particular, promoter allele P*0103 (G59029-T59353-T59356-A59402-C 59653) was largely restricted to black subjects. The promoter allele P*0202 (A59029-C59353-C59356-A59402-T 59653) was tightly linked to the slightly less frequent CCR2b-641, a variant of the CCR2b gene, which is about 12.7 kbp upstream from the promoter region. Another closely related promoter allele P*0201 (A59029-C59353-C59356-A59402-C 59653) exclusively carried the far less common CCR5-Δ32, a 32-bp deletion in the CCR5 coding sequence 2 kbp downstream from the promoter. The homozygous P*0201/*0201 genotype can be predicted as a risk factor for more rapid disease progression. Among human, chimpanzee, pig-tailed macaque, and sooty mangabey promoter allelic sequences, the apparent ancestral lineage of the promoter sequence (G59029-T59353-C59356-A59402-C 59653 = human P*0102) was highly conserved across the primate species analyzed here while P*0201 and P*0202 arose more recently than the other three major alleles. Further effort to establish the mechanism by which CCR chemokine receptor polymorphisms govern the initiation and pathogenesis of primate lentivirus infection apparently requires fully detailed genotypic characterization of the affected populations.",
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