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AIDS. 2000 Dec 1;14(17):2671-8.

Chemokine RANTES promoter polymorphism affects risk of both HIV infection and disease progression in the Multicenter AIDS Cohort Study.

Author information

1
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

OBJECTIVE:

To examine whether polymorphism in the RANTES gene is associated with HIV disease outcome.

DESIGN:

RANTES, a ligand of the major HIV co-receptor, CCR5, is known to block HIV-CCR5 interactions. Recently, two single nucleotide polymorphisms in the RANTES gene promoter region, designated -403G/A and -28C/G, have been described. Both polymorphisms can affect in-vitro promoter activity, and the RANTES -403A, -28G haplotype has been associated with a slower CD4 cell count decline rate in a Japanese cohort.

METHODS:

We compared RANTES compound genotype frequencies between HIV-positive and exposed-uninfected participants of the Multicenter AIDS Cohort Study (MACS) and rates of progression to AIDS for MACS seroconverters.

RESULTS:

We found that the two most common RANTES promoter compound genotypes, G1 (-403G/G, -28C/C) found in 67% of Caucasians, and G4 (-403G/A, -28C/C) found in 23% of Caucasians, were associated with altered risk of HIV transmission and progression, particularly in individuals who lacked the protective CCR5 mutation, CCR5delta32. In this study, individuals with a G4 compound genotype were more likely to acquire HIV than individuals with a G1 compound genotype (OR 1.72, P = 0.016) and the risk increased when individuals possessing CCR5delta32 were omitted from consideration (OR 2.13, P = 0.005). Among seroconverters lacking CCR5delta32, those who had the G4 compound genotype progressed significantly slower to AIDS-1993 than those with the G1 compound genotype (median time to AIDS 7.6 versus 5.4 years; RH 0.65; P = 0.007).

CONCLUSIONS:

These data implicate the RANTES-403A allele as a risk factor for HIV transmission and as a protective factor for HIV progression.

[Indexed for MEDLINE]

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