title: No relationship between TNF-α genetic variants and combination antiretroviral therapy-related lipodystrophy syndrome in HIV type 1-infected patients: a case-control study and a meta-analysis.
abstract: Tumor necrosis factor alpha (TNF-α) is thought to be involved in the pathogenic and metabolic events associated with HIV-1 infection. We assessed whether carriage of the TNF-α gene promoter single nucleotide polymorphism (SNP) is associated with lipodystrophy and metabolic derangements in HIV-1-infected patients treated with cART. We also assessed variations in TNF-α receptor plasma levels. The study group comprised 286 HIV-1-infected patients (133 with and 153 without lipodystrophy) and 203 uninfected controls (UC). TNF-α -238G > A, -308G > A, and -863 C > A SNP were assessed using PCR-RFLPs on white cell DNA. Plasma sTNF-α R1 and R2 levels were measured by ELISA. Student's t test, the χ(2) test, Pearson correlations, and the logistic regression test were performed for statistical analysis. The TNF-α -308G > A SNP was significantly associated with lipodystrophy in the univariate analysis (p = 0.04). This association, however, was no longer significant in the multivariate analysis. A meta-analysis of the published literature and our own data, which included 284 patients with lipodystrophy and 338 without lipodystrophy, showed that there was no relationship between the TNF-α -238G > A and -308G > A SNP and lipodystrophy (p > 0.05 for all comparisons). HIV-1-infected patients had greater sTNF-α R2 plasma levels than UC (p = 0.001) whereas sTNF-α R1 and R2 levels were not significantly different in both the HIV-1-infected cohorts, lipodystrophy vs. nonlipodystrophy (p = NS). In our cohort of white Spaniards the TNF-α -238G > A, -308G > A, and -863C > A SNP were not associated with lipodystrophy in HIV-1-infected patients treated with cART. This finding was replicated in a meta-analysis of the published data, which showed no associations between the TNF-α -238G > A and -308G > A SNP and lipodystrophy. In HIV-1-infected patients under cART there is a systemic overproduction of sTNF-α R2, which is unrelated to the presence of lipodystrophy.
authors.affiliation: Hospital Universitari de Tarragona Joan XXIII, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Veloso
authors.forename: Montserrat
authors.initials: M
authors.lastname: Olona
authors.forename: Joaquim
authors.initials: J
authors.lastname: Peraire
authors.forename: Consuelo
authors.initials: C
authors.lastname: Viladés
authors.forename: Pedro
authors.initials: P
authors.lastname: Pardo
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Victor
authors.initials: V
authors.lastname: Asensi
authors.forename: Montserrat
authors.initials: M
authors.lastname: Broch
authors.forename: Carmen
authors.initials: C
authors.lastname: Aguilar
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Dupla
authors.forename: Gerard
authors.initials: G
authors.lastname: Aragonés
authors.forename: Graciano
authors.initials: G
authors.lastname: Garcia-Pardo
authors.forename: Joan-Josep
authors.initials: JJ
authors.lastname: Sirvent
authors.forename: Joan
authors.initials: J
authors.lastname: Vendrell
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Richart
authors.forename: Francesc
authors.initials: F
authors.lastname: Vidal
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008060:Lipodystrophy / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D019380:Anti-HIV Agents; D014409:Tumor Necrosis Factor-alpha