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The effect of stromal cell-derived factor 1 (SDF1/CXCL12) genetic polymorphism on HIV-1 disease progression.

Abstract
The human immunodeficiency virus type 1 (HIV-1) epidemic is increasing in Brazil, and little information has been reported about the genetic host factors related to HIV-1 infection in the Brazilian population. A polymorphism in the conserved 3' untranslated region of the stromal cell-derived factor 1 (SDF1/CXCL12) gene has been related either to resistance to HIV-1 infection and delayed progression to AIDS or to rapid disease progression and death. A longitudinal study was conducted to evaluate the association of the SDF1 polymorphism and the progression of HIV-1 infection in 161 asymptomatic patients infected with HIV-1 (ASYMPT) and 617 patients with AIDS (SYMPT) from Londrina and the surrounding region, southern Brazil. The endpoints used were the development of AIDS, death, and the slopes of the CD4+ T cell counts and HIV-1 RNA plasma levels. Among the 161 ASYMPT patients, all of the 7 patients (4.3%) homozygous for the mutation remained asymptomatic (p=0.1906); 6 of them had not initiated antiretroviral therapy. Among the 617 patients with AIDS, 40 (6.5%) progressed to death. Of these, 33/388 (8.5%) did not have the SDF1-3'A allele, 6/196 (3.1%) were heterozygous and 1/33 (3.0%) was homozygous for the SDF1-3'A allele (p=0.029). The SDF1 genotypes were not associated with the surrogate markers of HIV-1 disease progression such as the CD4+ T cell decline and plasma HIV-1 RNA levels. The results observed in this study support the hypothesis that the mutation of SDF1-3'A could have a possible late-stage protective effect on HIV-1 disease progression in the Brazilian population.
AuthorsEdna Maria Vissoci Reiche, Maria Angelica Ehara Watanabe, Ana Maria Bonametti, Helena Kaminami Morimoto, Arilson Akira Morimoto, Susana Lilian Wiechmann, Jose Wander Breganó, Tiemi Matsuo, Fernando Vissoci Reiche, Helen Cristina Miranda, Karen Brajão Oliveira, Ingridt Hildegard Vogler, Alexandra Regina Siscar
JournalInternational journal of molecular medicine (Int J Mol Med) Vol. 18 Issue 4 Pg. 785-93 (Oct 2006) ISSN: 1107-3756 [Print] Greece
PMID16964435 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • RNA, Viral
Topics
  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Analysis of Variance
  • Brazil (epidemiology)
  • CD4 Lymphocyte Count
  • Chemokine CXCL12
  • Chemokines, CXC (genetics)
  • Disease Progression
  • Female
  • Gene Frequency
  • Genotype
  • HIV Infections (blood, epidemiology, genetics)
  • HIV-1 (genetics, growth & development)
  • Humans
  • Male
  • Middle Aged
  • Mutation (genetics)
  • Polymorphism, Genetic (genetics)
  • Polymorphism, Restriction Fragment Length
  • RNA, Viral (blood)

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