title: The effect of combined polymorphisms in chemokines and chemokine receptors on the clinical course of HIV-1 infection in a Brazilian population.
abstract: Polymorphisms in genes that encode chemokines or their receptors can modulate susceptibility to human immunodeficiency virus (HIV) infection and disease progression. The objective of this study was to assess the frequency of polymorphisms CCR5-Δ32, CCR2-64I, CCR5-59029A and SDF1-3'A and their role in the course of HIV infection in a Southern Brazilian population. Clinical data were obtained from 249 patients for an average period of 6.4 years and genotypes were determined by standard polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism. Survival analyses were conducted for three outcomes: CD4+ T-cell counts below 200 cells/µL, acquired immune deficiency syndrome (AIDS) or death. The frequency of the polymorphisms CCR5-Δ32, CCR2-64I, CCR5-59029A and SDF1-3'A were 0.024, 0.113, 0.487 and 0.207, respectively. CCR5-Δ32 was associated with a reduction in the risk for CD4+ T-cell depletion and with an increased risk for death after AIDS diagnosis. CCR2-64I was associated with a reduction in the risk for developing AIDS. SDF1-3'A was also associated with decreased risk for AIDS, but its effect was only evident when CCR2-64I was present as well. These results highlight the possibility of using these markers as indicators for the prognosis of disease progression and provide evidence for the importance of analysing the effects of gene polymorphisms in a combined fashion.
authors: Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, RS, Brasil.
authors: Valdimara Corrêa
authors: VC
authors: Vieira
authors: Maria Fernanda Martínez
authors: MF
authors: Barral
authors: Raul Andrés
authors: RA
authors: Mendoza-Sassi
authors: Jussara Maria
authors: JM
authors: Silveira
authors: Marcelo Alves
authors: MA
authors: Soares
authors: Ana Maria Barral
authors: AM
authors: de Martínez
mesh_terms: D000328:Adult; D054377:Chemokine CXCL12 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D054388:Receptors, CCR / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D054377:Chemokine CXCL12; D054388:Receptors, CCR