Genetic polymorphism of CCR5 gene and HIV disease: The heterozygous (CCR5/Δccr5) genotype is neither essential nor sufficient for protection against disease progression

Renate A. Morawetz, G. Paolo Rizzardi, Didier Glauser, Olivier Rutschmann, Bernard Hirschel, Luc Perrin, Milos Opravil, Markus Flepp, Jan Von Overbeck, Michel P. Glauser, Silvia Ghezzi, Elisa Vicenzi, Guido Poli, Adriano Lazzarin, Giuseppe Pantaleo

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)3223-3227
Number of pages5
JournalEuropean Journal of Immunology
Volume27
Issue number12
DOIs
Publication statusPublished - Dec 1997

Keywords

  • CCR-5 polymorphism
  • HIV disease progression
  • Long-term nonprogressor

ASJC Scopus subject areas

  • Immunology

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    Morawetz, R. A., Rizzardi, G. P., Glauser, D., Rutschmann, O., Hirschel, B., Perrin, L., Opravil, M., Flepp, M., Von Overbeck, J., Glauser, M. P., Ghezzi, S., Vicenzi, E., Poli, G., Lazzarin, A., & Pantaleo, G. (1997). Genetic polymorphism of CCR5 gene and HIV disease: The heterozygous (CCR5/Δccr5) genotype is neither essential nor sufficient for protection against disease progression. European Journal of Immunology, 27(12), 3223-3227. https://doi.org/10.1002/eji.1830271220