TY - JOUR
T1 - Chemokine RANTES promoter polymorphism affects risk of both HIV infection and disease progression in the Multicenter AIDS Cohort Study
AU - McDermott, David H.
AU - Beecroft, Matthew J.
AU - Kleeberger, Cynthia A.
AU - Al-Sharif, Fadwa M.
AU - Ollier, William E R
AU - Zimmerman, Peter A.
AU - Boatin, Boakye A.
AU - Leitman, Susan F.
AU - Detels, Roger
AU - Hajeer, Ali H.
AU - Murphy, Philip M.
N1 - UI - 21016129 LA - eng RN - 0 (RANTES) PT - Journal Article PT - Multicenter Study ID - 5-M01-RR-00052/RR/NCRR ID - UO1-AI-35042/AI/NIAID ID - UO1-AI-35043/AI/NIAID ID - etc DA - 20001226 IS - 0269-9370 SB - IM SB - X CY - England
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Chemokines
KW - Epidemiology
KW - Pathogenesis
KW - Risk factors
KW - Virus-cell interaction
U2 - 10.1097/00002030-200012010-00006
DO - 10.1097/00002030-200012010-00006
M3 - Article
SN - 0269-9370
VL - 14
SP - 2671
EP - 2678
JO - AIDS
JF - AIDS
IS - 17
ER -