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.
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.
Veloso
Sergi
S
Hospital Universitari de Tarragona Joan XXIII, Spain.
Olona
Montserrat
M
Peraire
Joaquim
J
Viladés
Consuelo
C
Pardo
Pedro
P
Domingo
Pere
P
Asensi
Victor
V
Broch
Montserrat
M
Aguilar
Carmen
C
López-Dupla
Miguel
M
Aragonés
Gerard
G
Garcia-Pardo
Graciano
G
Sirvent
Joan-Josep
JJ
Vendrell
Joan
J
Richart
Cristóbal
C
Vidal
Francesc
F
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*
D019380:Anti-HIV Agents; D014409:Tumor Necrosis Factor-alpha