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

David H. McDermott, Matthew J. Beecroft, Cynthia A. Kleeberger, Fadwa M. Al-Sharif, William E R Ollier, Peter A. Zimmerman, Boakye A. Boatin, Susan F. Leitman, Roger Detels, Ali H. Hajeer, Philip M. Murphy

    Research output: Contribution to journalArticlepeer-review

    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, CCR5Δ32. 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 CCR5Δ32 were omitted from consideration (OR 2.13, P = 0.005). Among seroconverters lacking CCR5Δ32, 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. © 2000 Lippincott Williams & Wilkins.
    Original languageEnglish
    Pages (from-to)2671-2678
    Number of pages7
    JournalAIDS
    Volume14
    Issue number17
    DOIs
    Publication statusPublished - 2000

    Keywords

    • Chemokines
    • Epidemiology
    • Pathogenesis
    • Risk factors
    • Virus-cell interaction

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