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 geneticpolymorphisms on antiretroviral therapy (ART)-associated lipodystrophy. We includedin the study 255 ICoNA. patients and we assessed the distribution of Fas 670 AGpolymorphism, ApoC3 455 CT and 482 CT polymorphisms, C161T silent substitutionin the PPAR g gene, the Adrenergic b3 Receptor (ARb3) codon 64 TC variant, andtwo polymorphisms in the Adrenergic b2 Receptor (ARb2) codon 16 AG and codon 27CG. Crude rates of lipoatrophy and fat accumulation and adjusted relative rates werecalculated using Poisson regression.Results: In a multivariate model after adjusting for gender, HIV exposure, age, currentviral load, hepatitis C virus (HCV) serology, nucleoside reverse-transcriptase inhibitor(NRTI) pair/‘third drugs’ currently used, months of pre-highly active antiretroviraltherapy (HAART) exposures to NRTI, the following genotypes resulted protectiveagainst lipoatrophy: ApoC3 455 CC genotype [adjusted relative risks (ARR) 0.2,95% confidence interval (CI) 0.046–0.91 vs CT/TT, P¼0.037], ARb3 codon 64 TTgenotype (ARR 0.39, 95% CI 0.14–1.06 vs TC/CC, P¼0.066), and Fas 670 GGgenotype (ARR 0.51, 95% CI 0.26–1.01 vs AG/AA, P¼0.053). With regard to fataccumulation, in the multivariate model, the ARb2 codon 27 CC genotype resultedprotective (ARR 0.21, 95% CI 0.08–0.51 vs CG/GG, P¼0.0006), whereas the ARb2codon 16 AA genotype resulted associated with higher risk (ARR 3.72, 95% CI 1.58–8.76 vs AG/GG, P¼0.0026).Conclusion: Our study suggests that genetic polymorphisms of genes involved inapoptosis and adipocyte metabolism are significantly related to ART associated lipodystrophy.Particularly, we evidenced a role for ApoC3 455 in lipoatrophy and for thetwo variants of ARb2 in fat accumulation.