No relationship between TNF-alpha 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-alpha) is thought to be involved in the pathogenic and metabolic events associated with HIV-1 infection. We assessed whether carriage of the TNF-alpha 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-alpha receptor plasma levels. The study group comprised 286 HIV-1-infected patients (133 with and 153 without lipodystrophy) and 203 uninfected controls (UC). TNF-alpha -238G > A, -308G > A, and -863 C > A SNP were assessed using PCR-RFLPs on white cell DNA. Plasma sTNF-alpha R1 and R2 levels were measured by ELISA. Student’s t test, the chi² test, Pearson correlations, and the logistic regression test were performed for statistical analysis. The TNF-alpha -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-alpha -238G > A and -308G > A SNP and lipodystrophy (p > 0.05 for all comparisons). HIV-1-infected patients had greater sTNF-alpha R2 plasma levels than UC (p = 0.001) whereas sTNF-alpha 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-alpha -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-alpha -238G > A and -308G > A SNP and lipodystrophy. In HIV-1-infected patients under cART there is a systemic overproduction of sTNF-alpha R2, which is unrelated to the presence of lipodystrophy.

• Determinants of Health
  • Other
• Population(s)
  • General HIV+ population
• Engagement and Care Cascade
  • Treatment
• Co-morbidities
  • Other