Effect of TNF-a genetic variants and CCR5 Delta 32 on the vulnerability to HIV-1 infection and disease progression in Caucasian Spaniards
Por:
Veloso, S, Olona, M, Garcia, F, Domingo, P, Alonso-Villaverde, C, Broch, M, Peraire, J, Vilades, C, Plana, M, Pedrol, E, Lopez-Dupla, M, Aguilar, C, Gutierrez, M, Leon, A, Tasias, M, Gatell, JM, Richart, C, Vidal, F
Publicada:
26 abr 2010
Resumen:
Background: Tumor necrosis factor alpha (TNF-a) is thought to be involved in the various immunogenetic events that influence HIV-1 infection.
Methods: We aimed to determine whether carriage of the TNF-a-238G>A, -308G>A and -863C>A gene promoter single nucleotide polymorphisms (SNP) and the CCR5 Delta 32 variant allele influence the risk of HIV-1 infection and disease progression in Caucasian Spaniards. The study group consisted of 423 individuals. Of these, 239 were uninfected (36 heavily exposed but uninfected [EU] and 203 healthy controls [HC]) and 184 were HIV-1-infected (109 typical progressors [TP] and 75 long-term nonprogressors [LTNP] of over 16 years' duration). TNF-a SNP and the CCR5 Delta 32 allele were assessed using PCR-RFLP and automatic sequencing analysis methods on white blood cell DNA. Genotype and allele frequencies were compared using the X-2 test and the Fisher exact test. Haplotypes were compared by logistic regression analysis.
Results: The distribution of TNF-a-238G>A, -308G>A and -863C>A genetic variants was non-significantly different in HIV-1-infected patients compared with uninfected individuals: -238G>A, p = 0.7 and p = 0.3; -308G>A, p = 0.05 and p = 0.07; -863C>A, p = 0.7 and p = 0.4, for genotype and allele comparisons, respectively. Haplotype analyses, however, indicated that carriers of the haplotype H3 were significantly more common among uninfected subjects (p = 0.04). Among the infected patients, the distribution of the three TNF-a genetic variants assessed was non-significantly different between TP and LTNP: -238G>A, p = 0.35 and p = 0.7; -308G>A, p = 0.7 and p = 0.6: -863C>A, p = 0.2 and p = 0.2, for genotype and allele comparisons, respectively. Haplotype analyses also indicated non-significant associations. Subanalyses in the LTNP subset indicated that the TNF-a-238A variant allele was significantly overrepresented in patients who spontaneously controlled plasma viremia compared with those who had a detectable plasma viral load (genotype comparisons, p = 0.02; allele comparisons, p = 0.03). The CCR5 Delta 32 distribution was non-significantly different in HIV-1-infected patients with respect to the uninfected population (p = 0.15 and p = 0.2 for genotype and allele comparisons, respectively) and in LTNP vs TP (p = 0.4 and p = 0.5 for genotype and allele comparisons, respectively).
Conclusions: In our cohort of Caucasian Spaniards, TNF-a genetic variants could be involved in the vulnerability to HIV-1 infection. TNF-a genetic variants were unrelated to disease progression in infected subjects. The -238G>A SNP may modulate the control of viremia in LTNP. Carriage of the CCR5 Delta 32 variant allele had no effect on the risk of infection and disease progression.
Filiaciones:
Veloso, S:
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
IISPV, Tarragona, Spain
Univ Rovira & Virgili, Tarragona, Spain
Olona, M:
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
IISPV, Tarragona, Spain
Univ Rovira & Virgili, Tarragona, Spain
Garcia, F:
Hosp Clin Barcelona, Barcelona, Spain
Domingo, P:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Univ Autonoma Barcelona, E-08193 Barcelona, Spain
Alonso-Villaverde, C:
IISPV, Tarragona, Spain
Univ Rovira & Virgili, Tarragona, Spain
Hosp Univ St Joan, Reus, Spain
Broch, M:
IISPV, Tarragona, Spain
Univ Rovira & Virgili, Tarragona, Spain
Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr CB06 03, Madrid, Spain
Peraire, J:
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
IISPV, Tarragona, Spain
Univ Rovira & Virgili, Tarragona, Spain
Vilades, C:
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
IISPV, Tarragona, Spain
Univ Rovira & Virgili, Tarragona, Spain
Plana, M:
Hosp Clin Barcelona, Barcelona, Spain
Pedrol, E:
Hosp St Pau & Santa Tecla, Tarragona, Spain
Lopez-Dupla, M:
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
IISPV, Tarragona, Spain
Univ Rovira & Virgili, Tarragona, Spain
Aguilar, C:
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
IISPV, Tarragona, Spain
Univ Rovira & Virgili, Tarragona, Spain
Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr CB06 03, Madrid, Spain
Gutierrez, M:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Leon, A:
Hosp Clin Barcelona, Barcelona, Spain
Tasias, M:
Hosp St Pau & Santa Tecla, Tarragona, Spain
Gatell, JM:
Univ Barcelona, Barcelona, Spain
Richart, C:
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
IISPV, Tarragona, Spain
Univ Rovira & Virgili, Tarragona, Spain
Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr CB06 03, Madrid, Spain
Vidal, F:
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
IISPV, Tarragona, Spain
Univ Rovira & Virgili, Tarragona, Spain
Gold, Green Published
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