Effect of chemokine receptor gene polymorphisms on the clinical course of HIV-1 infection in Brazilians patients
V. Correa Vieira1, R. Mendoza-Sassi1, J. Silveira1, M. Alves Soares2, A.M. Barral de Martinez1
1Universidade Federal do Rio Grande, Rio Grande, Brazil, 2Universidade Federal do Rio de Janeiro, Departamento de Genética, Rio de Janeiro, Brazil
Background: Chemokine receptors are essential co-receptors for human immunodeficiency virus (HIV) entry into target cells. Mutations in genes encoding chemokine receptors and their ligands can alter susceptibility to HIV infection and disease progression. The CCR5Δ32 and CCR2-64I mutations are associated with delayed progression to AIDS, while CCR5-59029A was found to accelerate disease progression. The role of CCR2-64I and CCR5-59029A polymorphisms has not been confirmed in all studies performed. And their phenotypic effects may vary among distinct populations. Thus, the aim of this study was to investigate the role of CCR5Δ32, CCR2-64I and CCR5-59029A polymorphisms in the clinical course of HIV-1 infection in a Brazilian population.
Methods: Blood samples were collected from 249 patients followed up at the university hospital of Universidade Federal do Rio Grande. Genotyping was performed by PCR and PCR-RFLP. Clinical data were obtained from patient's records for a median period of 6.44 years. The Cox proportional hazards model was used to evaluate the prognostic value of the mutations for CD4+ T-cells counts below 200cells/mm3; AIDS, according to the Brazilian Ministry of Health criteria and death.
Results: The CCR5-Δ32 allele was associated with a 75% reduction in the risk of progression to CD4+ counts below 200 cells/mm3 (p=0.04) and a 36% reduction in the risk AIDS (p=0.15). The CCR2-64I allele was associated with a 35% reduction in the risk of a AIDS (p=0.015). The presence of these polymorphisms did not alter the rate of progression to death. The CCR5-59029A had no significant association with the clinical course of infection.
Conclusions: These results confirm the protective effect of CCR5-Δ32 and CCR2-64I in early stages of HIV infection in this Brazilian population. Highlighting the importance of investigating the role of these polymorphisms in different populations and its potential role for use as prognostics markers.
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