Open Access Research article

Effect of TNF-α genetic variants and CCR5Δ32 on the vulnerability to HIV-1 infection and disease progression in Caucasian Spaniards

Sergi Veloso123, Montserrat Olona123, Felipe García4, Pere Domingo56, Carlos Alonso-Villaverde237, Montserrat Broch238, Joaquim Peraire123, Consuelo Viladés123, Montserrat Plana4, Enric Pedrol9, Miguel López-Dupla123, Carmen Aguilar1238, Mar Gutiérrez5, Agathe Leon4, Mariona Tasias9, Josep Ma Gatell104, Cristóbal Richart1238 and Francesc Vidal123*

Author Affiliations

1 Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain

2 IISPV, Tarragona, Spain

3 Universitat Rovira i Virgili, Tarragona, Spain

4 Hospital Clínic, Barcelona, Spain

5 Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

6 Universitat Autònoma de Barcelona, Barcelona, Spain

7 Hospital Universitari de Sant Joan, Reus, Spain

8 CIBER Fisiopatologia de la Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Madrid, Spain

9 Hospital de Sant Pau i Santa Tecla, Tarragona, Spain

10 Universitat de Barcelona, Barcelona, Spain

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BMC Medical Genetics 2010, 11:63  doi:10.1186/1471-2350-11-63

Published: 26 April 2010



Tumor necrosis factor alpha (TNF-α) is thought to be involved in the various immunogenetic events that influence HIV-1 infection.


We aimed to determine whether carriage of the TNF-α-238G>A, -308G>A and -863 C>A gene promoter single nucleotide polymorphisms (SNP) and the CCR5Δ32 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-α SNP and the CCR5Δ32 allele were assessed using PCR-RFLP and automatic sequencing analysis methods on white blood cell DNA. Genotype and allele frequencies were compared using the χ 2 test and the Fisher exact test. Haplotypes were compared by logistic regression analysis.


The distribution of TNF-α-238G>A, -308G>A and -863 C>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; -863 C>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-α 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: -863 C>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-α-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 CCR5Δ32 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).


In our cohort of Caucasian Spaniards, TNF-α genetic variants could be involved in the vulnerability to HIV-1 infection. TNF-α 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 CCR5Δ32 variant allele had no effect on the risk of infection and disease progression.