The effect of stromal cell-derived factor 1 (SDF1/CXCL12) genetic polymorphism on HIV-1 disease progression.
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.
Reiche
Edna Maria Vissoci
EM
Health Sciences Center, University Hospital of Londrina State University, CEP 86.038-440, Londrina, Paraná, Brazil. reiche@sercomtel.com.br
Ehara Watanabe
Maria Angelica
MA
Bonametti
Ana Maria
AM
Kaminami Morimoto
Helena
H
Akira Morimoto
Arilson
A
Wiechmann
Susana Lilian
SL
Breganó
Jose Wander
JW
Matsuo
Tiemi
T
Vissoci Reiche
Fernando
F
Miranda
Helen Cristina
HC
Brajão Oliveira
Karen
K
Vogler
Ingridt Hildegard
IH
Siscar
Alexandra Regina
AR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D001938:Brazil / Q000453:epidemiology; D018791:CD4 Lymphocyte Count; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012367:RNA, Viral / Q000097:blood
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D012367:RNA, Viral