title: PPARgamma Pro12Ala polymorphism in HIV-1-infected patients with HAART-related lipodystrophy.
abstract: Peroxisome proliferator-activated receptor gamma (PPARgamma) is involved in obesity and in some components of the metabolic syndrome in unselected population. To determine whether PPARgamma genetic variants are associated with the risk of developing lipodystrophy and its associated metabolic disturbances in HIV-1-infected patients treated with HAART and to assess PPARgamma mRNA expression in subcutaneous adipose tissue (SAT). The study group comprised 278 patients infected with HIV-1 and treated with antiretroviral drugs (139 with lipodystrophy and 139 without) and 105 uninfected controls (UC). The PPARgamma Pro12Ala (C%>G) single nucleotide polymorphism (SNP) was assessed using PCR-RFLPs on white cell DNA. PPARgamma mRNA expression in SAT was assessed in 38 patients (25 with lipodystrophy and 13 without) and in 21 UC by real-time PCR. Statistical analysis was based on Student's T tests, Chi(2) tests, Spearman's correlations tests and logistic regression tests. PPARgamma Pro12Ala genotype distribution and allele frequencies were non-significantly different between both HIV-1-infected categories, lipodystrophy vs non-lipodystrophy (p=0.9 and p=0.87, respectively). Lipodystrophic patients harbouring the rare X/Ala genotype (Ala/Ala plus Pro/Ala) had significantly greater plasma total and LDL cholesterol levels compared with carriers of the common Pro/Pro genotype (p=0.029 and p=0.016, respectively) at univariate analyses. At multivariate analyses these associations were no longer significant. There was a near-significant decreased SAT PPARgamma mRNA expression in patients with lipodystrophy compared to UC (p=0.054). PPARgamma Pro12Ala SNP has no effect on the risk of developing lipodystrophy in HIV-1-infected patients treated with HAART. PPARgamma mRNA SAT expression appears decreased in lipodystrophy.
authors.affiliation: Hospital Universitari Joan XXIII, Tarragona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Saumoy
authors.forename: Sergi
authors.initials: S
authors.lastname: Veloso
authors.forename: Carlos
authors.initials: C
authors.lastname: Alonso-Villaverde
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Matilde R
authors.initials: MR
authors.lastname: Chacón
authors.forename: Merce
authors.initials: M
authors.lastname: Miranda
authors.forename: Gerard
authors.initials: G
authors.lastname: Aragonès
authors.forename: Maria Mar
authors.initials: MM
authors.lastname: Gutiérrez
authors.forename: Consuelo
authors.initials: C
authors.lastname: Viladés
authors.forename: Joaquim
authors.initials: J
authors.lastname: Peraire
authors.forename: Joan-Josep
authors.initials: JJ
authors.lastname: Sirvent
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Dupla
authors.forename: Carmen
authors.initials: C
authors.lastname: Aguilar
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Richart
authors.forename: Francesc
authors.initials: F
authors.lastname: Vidal
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008060:Lipodystrophy / Q000139:chemically induced* / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D047495:PPAR gamma