In:
BMC Medical Genetics, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2010-12)
Abstract:
Tumor necrosis factor alpha (TNF-α) 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-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. Results 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). Conclusions 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.
Type of Medium:
Online Resource
ISSN:
1471-2350
DOI:
10.1186/1471-2350-11-63
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2010
detail.hit.zdb_id:
2041359-2
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