Stromal cell‐derived factor 1 (SDF1) genetic polymorphism in a sample of healthy individuals, seronegative individuals exposed to human immunodeficiency virus type 1 (HIV‐1) and patients infected with HIV‐1 from the Brazilian population

Abstract

The interaction of viral and host factors is believed to determine not only the risk for initial human immunodeficiency virus type 1 (HIV-1) acquisition but also the course of the infection. Genetic polymorphisms in the chemokine receptors and their ligands were related to the susceptibility and resistance to HIV-1 infection. A polymorphism in the conserved 3' untranslated region of the stromal cell-derived factor-1 (SDF1) gene, which encodes a ligand of the CXCR4 receptor, has been related either to delayed progression to AIDS or to rapid disease progression and death. Global, regional, and ethnic distributions of frequencies of SDF1 genotypes and of the SDF1-3'A allele vary significantly. Although the HIV-1 epidemic is increasing in Brazil, little information about the frequencies of host genetic mutations related to HIV/AIDS resistance in the Brazilian population has been reported. To address this question, this study was carried out in order to determine the frequencies of the SDF1 polymorphism and the SDF1-3'A allele on 1061 genomic DNA samples purified from peripheral blood cells of 136 healthy individuals (group 1), 147 HIV-1-exposed seronegative individuals (group 2), 161 HIV-1-infected asymptomatic individuals and with CD4(+) T-cells count 350 mm(-3) (group 3), and 617 HIV-1-infected individuals with AIDS and/or CD4(+) T-cells count < 350 mm(-3) (group 4). The frequencies of the SDF1-3'A homozygous mutation were 3.7%, 6.1%, 4.3%, and 5.3% among groups 1, 2, 3, and 4, respectively (P = 0.5120). The overall frequency of the SDF1-3'A allele was 0. 1984 and did not differ among the four groups (P = 0.2744). The results underscore the global distribution of the SDF1 polymorphism and the hypothesis that the SDF1-3'A allele, itself, may not be sufficient to prevent the risk of HIV-1 infection and may be not related to the progression of the disease in the Brazilian population.

HIV-1 Infection: The Functional Importance of SDF1, CCR2 and CCR5 in Protection and Therapeutics

“…Health Care Current SDF1 3' A mutation potentially involved in protection against late stage of HIV1 stimulated disease [7]. The fact further can be supported from in vitro studies on peripheral blood mononuclear cells from ASYMPT and SYMPT patients where PBMCs from HIV1 carrier ASYMT patients express higher amount of SDF1.…”

“…Since SDF1 is a minor allele, population with lower minor allele frequency of this allele have lower resistance against HIV1 progression after infection [6]. The SDF1 genotyping study conducted on Brazilian population covering 161 asymptomatic patients harbouring HIV1 infection (ASYMPT) versus 617 patients with AIDS status (SYMPT) shows that individuals harbouring homozygous allele for SDF1 (3' A) either does not progress to the stage of AIDS and does not die from AIDS if retroviral therapy is availed suggest that presence of SDF1 3' A mutation potentially involved in protection against late stage of HIV1 stimulated disease [7]. The fact further can be supported from in vitro studies on peripheral blood mononuclear cells from ASYMPT and SYMPT patients where PBMCs from HIV1 carrier ASYMT patients express higher amount of SDF1.…”

The effect of combined polymorphisms in chemokines and chemokine receptors on the clinical course of HIV-1 infection in a Brazilian population

“…However, other studies did not find such a correlation (Ioannidis et al 2001, Watanabe et al 2003, Reiche et al 2006, while a third group of studies found a correlation with accelerated disease progression (Mummidi et al 1998, van Rij et al 1998, Daar et al 2005. SDF1-3'A distribution varies significantly between different populations, with frequencies from 2-9% in Africans and up to 54-71% in Oceania (Su et al 1999).…”

“…The Brazilian population presents a complex genetic background, characterised by a high degree of miscegenation (Callegari-Jacques et al 2003, Pena 2005. In major Brazilian cities, CCR5-∆32 was found at frequencies of between 2-7% (Munerato et al 2003, Vargas et al 2006, Reiche et al 2008, Rigato et al 2008, CCR5-59029A between 39-44% (Rigato et al 2008), CCR2-64I at approximately 10% (Munerato et al 2003, Rigato et al 2008) and SDF1-3'A between 18-22% (Reiche et al 2006, Rigato et al 2008. Despite the moderate rates of HIV infection reported in Brazil, little is known about the influence of genetic polymorphisms on HIV disease progression in this population.…”

Analysis of Immunological, Viral, Genetic, and Environmental Factors That Might Be Associated with Decreased Susceptibility to HIV Infection in Serodiscordant Couples in Florianópolis, Southern Brazil

“…4 Although Brazil has the largest number of HIV-infected people among the countries in Central and South America, 5 and an ethnically very diverse population, 6 there is a paucity of information regarding cohorts of serodiscordant couples. The few reports on this subject in Brazil have addressed genetic polymorphisms in CXCL12 7 and CCR5, 2 the presence of specific HLA alleles, 8 patterns of activation in CD4 + T and CD8 + T lymphocytes, 9 sexual transmission profiles, 10 or sociodemographic characteristics associated with HIV infection. 9 Reports evaluating cellular host proteins that interact with HIV during its replication cycle have not yet been published.…”