Genetic polymorphisms differently influencing the emergence of atrophy and fat accumulation in HIV-related lipodystrophy

OBJECTIVE AND DESING: 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 substituion in the PPAR gamma gene, the Adrenergic beta3 REceptor (ARbeta3) codon 64 TC variant, and two polymorphisms in the Adrenergic beta2 Receptor (ARbeta2) codon 16 AG and docon 27 CG. Crude rates of lipoatrophy and fat accumulation and adjusted relative rates were calculated using Poisson regression. RESULTS: In a multivariate model afer 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) 0.046-0.91vs CT/TT, P = 0.037), ARbeta2 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 ARbeta2 codon 27 CC genotype resulted protective (ARR 0.21, 95% CI 0.08-0.51 vs CG/GG, P = 0.0006) whereas the ARbeta 2 codon 16AA 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 of ApoC3 -456 in lipoatrophy and for the two variantes of ARbeta2 in fat accumulation.