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

AIDS. 2000 Dec 1;14(17):2671-8. doi: 10.1097/00002030-200012010-00006.

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.

Publication types

  • Multicenter Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acquired Immunodeficiency Syndrome / diagnosis
  • Acquired Immunodeficiency Syndrome / epidemiology
  • Acquired Immunodeficiency Syndrome / genetics
  • Acquired Immunodeficiency Syndrome / transmission
  • Africa / epidemiology
  • Alleles
  • Chemokine CCL5 / genetics*
  • Cohort Studies
  • Continental Population Groups / genetics
  • Disease Progression
  • Ethnic Groups / genetics
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease / genetics*
  • HIV Infections / diagnosis
  • HIV Infections / epidemiology
  • HIV Infections / genetics*
  • HIV Infections / transmission*
  • HIV Seropositivity / diagnosis
  • HIV Seropositivity / epidemiology
  • HIV Seropositivity / genetics
  • HIV Seropositivity / transmission
  • Haplotypes / genetics
  • Humans
  • North America / epidemiology
  • Polymorphism, Genetic / genetics*
  • Prognosis
  • Promoter Regions, Genetic / genetics*
  • Survival Rate

Substances

  • Chemokine CCL5