TY - JOUR
T1 - Genetic polymorphism of CCR5 gene and HIV disease
T2 - The heterozygous (CCR5/Δccr5) genotype is neither essential nor sufficient for protection against disease progression
AU - Morawetz, Renate A.
AU - Rizzardi, G. Paolo
AU - Glauser, Didier
AU - Rutschmann, Olivier
AU - Hirschel, Bernard
AU - Perrin, Luc
AU - Opravil, Milos
AU - Flepp, Markus
AU - Von Overbeck, Jan
AU - Glauser, Michel P.
AU - Ghezzi, Silvia
AU - Vicenzi, Elisa
AU - Poli, Guido
AU - Lazzarin, Adriano
AU - Pantaleo, Giuseppe
PY - 1997/12
Y1 - 1997/12
N2 - Homozygous (Δccr5/Δccr5) and heterozygous (CCR5/Δccr5) deletions in the β-chemokine receptor 5 (CCR5) gene, which encodes for the major co-receptor for macrophage-tropic HIV-1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/ Δccr5 genotype was found more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p <0.0001), in agreement with previous studies. Kaplan-Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4+ T cell counts > 500/μl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/Δccr5 genotype. However, when LTNP were analyzed separetely, no significant differences in CD4+ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild-type (69% of LTNP) and the heterozygous (31.0%) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/Δccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/Δccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.
AB - Homozygous (Δccr5/Δccr5) and heterozygous (CCR5/Δccr5) deletions in the β-chemokine receptor 5 (CCR5) gene, which encodes for the major co-receptor for macrophage-tropic HIV-1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/ Δccr5 genotype was found more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p <0.0001), in agreement with previous studies. Kaplan-Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4+ T cell counts > 500/μl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/Δccr5 genotype. However, when LTNP were analyzed separetely, no significant differences in CD4+ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild-type (69% of LTNP) and the heterozygous (31.0%) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/Δccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/Δccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.
KW - CCR-5 polymorphism
KW - HIV disease progression
KW - Long-term nonprogressor
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U2 - 10.1002/eji.1830271220
DO - 10.1002/eji.1830271220
M3 - Article
C2 - 9464809
AN - SCOPUS:0031445262
VL - 27
SP - 3223
EP - 3227
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 12
ER -