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Adverse effect of the CCR5 promoter −2459A allele on HIV‐1 disease progression
Author(s) -
Knudsen Troels B.,
Kristiansen Thomas B.,
Katzenstein Terese L.,
EugenOlsen Jesper
Publication year - 2001
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.2054
Subject(s) - allele , genotype , biology , chemokine receptor ccr5 , ccr2 , genetics , gene , receptor , chemokine receptor , chemokine
HIV positive individuals heterozygous for a 32 basepair deletion in the CCR5 encoding gene (CCR5 Δ32) have a reduced number of CCR5 receptors on the cell surface and a slower progression towards AIDS and death. Other human polymorphisms, such as the CCR2 64I and the CCR5 promoter −2459 A/G transition that has been discovered recently, have also been shown to influence HIV progression. Since genetic linkages make these polymorphisms interdependent variables, the aim of the present study was to isolate and evaluate the effect on HIV disease progression for each of these mutations independently. Genotypes were determined in 119 individuals enrolled in the Copenhagen AIDS Cohort. When including the concurrent effects of the CCR5 Δ32 and CCR2 64I mutations, homozygous carriers of the CCR5 promoter −2459A allele had a significantly faster progression towards death than heterozygous A/G individuals ( P = 0.03), whereas this adverse effect was not significant when comparing A/A and G/G individuals. However, independent analysis revealed a significant adverse effect of the CCR5 promoter −2459A allele. Homozygous carriers of the −2459A allele that lack the protective effects of the CCR5 Δ32 and CCR2 64I mutations were found to have a median survival of 6.0 years, whereas carriers of the −2459G allele had a median survival of 9.4 years ( P < 0.01). J. Med. Virol. 65:441–444, 2001. © 2001 Wiley‐Liss, Inc.