SDF1-3'A polymorphism and its association with the course of infection in HIV-1
positive patients from the Hospital of Federal University of Rio Grande
(HU-FURG) in the Southern of Brazil
M.F. Martinez Barral, V. Côrrea Vieira, R. Mendoza-Sassi, J. Silveira, A.M. Barral de Martinez
Federal University of Rio Grande, Rio Grande, Brazil
Background: Stromal-derived factor
(SDF-1) is the natural ligand for CXCR4, a fusion coreceptor for lymphotropic
strains (X4) of Human immunodeficiency virus 1 (HIV-1). Genetic polymorphism in
the ligand SDF-1 may be related to the risk of infection and progression to
AIDS and death. The G to A transition in the 3'UTR
of the SDF-1 gene leads to polymorphism referred to as SDF1-3'A. Homozigosity for the mutation has initially
shown to be associated with delayed disease progression in the course of HIV-1
infection. In contrast to that, other studies have been demonstrating a more
rapid disease and death progression in individuals with the SDF1-3'A/3'A
genotype. This study was carried out to determine the prevalence of this
polymorphism and its association with the course of infection in HIV-1 positive
patients, in the Hospital of Federal University of Rio Grande.
Methods: Genomic DNA was extracted
from blood samples using commercial kit. Genotyping was performed by polymerase
chain reaction (PCR) and restriction fragment length polymorphism (RFLP).
Survival analyses were conducted for three endpoints: CD4+ T-cells counts below
200/ml; AIDS; and death. For statistical analysis STATA 8.0 was used.
total of 231 individuals were genotyped. The frequency of the
SDF1-3'A homozygous mutation was 1.73% (n=4) and heterozygous mutation was
38.1% (n=88). Individuals carrying the SDF1-3'A mutation in homozygosis had a
higher risk of progressing to AIDS (RH = 1.63, p=0.025).
Conclusions: Studies have been showing
that individuals with the SDF1-3'A/3'A genotype have a decreased SDF-1
expression, which might be associated with a higher emergency of X4 viruses. If
true, this effect can explain why individuals with the polymorphism in homozygosis
progress more rapidly to AIDS. More analysis are necessary to elucidate the
function of the polymorphism SDF1-3'A on the course of infection, in order to
use this knowledge for new antiretroviral drugs production.
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