Genetic polymorphisms differently influencing the emergence of 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 gamma gene, the Adrenergic beta 3 Receptor (AR beta 3) codon 64 TC variant, and two polymorphisms in the Adrenergic beta 2 Receptor (AR beta 2) 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], AR beta 3 codon 64 TT genotype (ARR 0.39, 95% Cl 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 AR beta 2 codon 27 CC genotype resulted protective (ARR 0.21, 95% CI 0.08-0.51 vs CG/GG, P=0.0006), whereas the AR beta 2 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 lipoatrophyandforthe two variants of AR beta 2 in fat accumulation.