Polymorphisms in genes involved in lipid metabolism and apoptosis differently influence atrophy and fat accumulation in HIV related lipodystrophy

OBJECTIVE AND DESIGN: The present study aims at evaluating the influence of genetic polymorphisms on antiretroviral therapy (ART)-associated lipodystrophy. We included in the study 255 ICoNA. patients and we assessed the distribution of Fas -670 AG polymorphism, ApoC3 -455 CT and -482 CT polymorphisms, C161T silent substitution in the PPAR γ gene, the Adrenergic β3 Receptor (ARβ3) codon 64 TC variant, and two polymorphisms in the Adrenergic β2 Receptor (ARβ2) codon 16 AG and codon 27 CG. Crude rates of lipoatrophy and fat accumulation and adjusted relative rates were calculated using Poisson regression. RESULTS: In a multivariate model after adjusting for gender, HIV exposure, age, current viral load, hepatitis C virus (HCV) serology, nucleoside reverse-transcriptase inhibitor (NRTI) pair/?third drugs? currently used, months of pre-highly active antiretroviral therapy (HAART) exposures to NRTI, the following genotypes resulted protective against lipoatrophy: ApoC3 -455 CC genotype [adjusted relative risks (ARR) 0.2, 95% confidence interval (CI) 0.046-0.91 vs CT/TT, P ≤ 0.037], ARβ3 codon 64 TT genotype (ARR 0.39, 95% CI 0.14-1.06 vs TC/CC, P ≤ 0.066), and Fas -670 GG genotype (ARR 0.51, 95% CI 0.26-1.01 vs AG/AA, P ≤ 0.053). With regard to fat accumulation, in the multivariate model, the ARβ2 codon 27 CC genotype resulted protective (ARR 0.21, 95% CI 0.08-0.51 vs CG/GG, P ≤ 0.0006), whereas the ARβ2 codon 16 AA genotype resulted associated with higher risk (ARR 3.72, 95% CI 1.58-8.76 vs AG/GG, P ≤ 0.0026). CONCLUSION: Our study suggests that genetic polymorphisms of genes involved in apoptosis and adipocyte metabolism are significantly related to ART associated lipodystrophy. Particularly, we evidenced a role for ApoC3 -455 in lipoatrophy and for the two variants of ARβ2 in fat accumulation.