title: Genetic polymorphisms differently influencing the emergence of atrophy and fat accumulation in HIV-related lipodystrophy.
abstract: OBJECTIVE
  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 beta3 Receptor (ARbeta3) codon 64 TC variant, and two polymorphisms in the Adrenergic beta2 Receptor (ARbeta2) 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], ARbeta3 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 ARbeta2 codon 16 AA genotype resulted associated with higher risk (ARR 3.72, 95% CI 1.58-8.76 vs AG/GG, P = 0.0026).
  
  
  CONCLUSIONS
  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 ARbeta2 in fat accumulation.
authors.affiliation: Department of Clinical Sciences, 'Luigi Sacco' Hospital, University of Milan, Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zanone Poma
authors.forename: Agostino
authors.initials: A
authors.lastname: Riva
authors.forename: Milena
authors.initials: M
authors.lastname: Nasi
authors.forename: Paola
authors.initials: P
authors.lastname: Cicconi
authors.forename: Valentina
authors.initials: V
authors.lastname: Broggini
authors.forename: Alessandro Cozzi
authors.initials: AC
authors.lastname: Lepri
authors.forename: Daniela
authors.initials: D
authors.lastname: Mologni
authors.forename: Francesco
authors.initials: F
authors.lastname: Mazzotta
authors.forename: Antonella D'Arminio
authors.initials: AD
authors.lastname: Monforte
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
authors.forename: Massimo
authors.initials: M
authors.lastname: Galli