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.