Peroxisome Proliferator Activating Receptor Alpha and Gamma Polymorphisms and Metabolic Abnormalities in HIV-Infected Patients Receiving Highly Active Antiretroviral Therapy: The ANRS CO8 APROCO-COPILOTE Study

Abstract

Highly active antiretroviral therapy (HAART) is associated with fat redistribution and metabolic disorders. The present study was undertaken to evaluate the association between peroxisome proliferator activated receptor (PPAR)α and PPARγ polymorphisms, two genes involved in lipid metabolism and adipocyte differentiation, and elements of the metabolic syndrome, lipodystrophy, or carbohydrate metabolism abnormalities in patients receiving HAART. The frequency distribution of rare alleles for PPARα (L162V) and PPARγ (P12A and H449H) was compared using the chi square test in 363 HIV-1-infected patients classified according to the presence or absence of the metabolic syndrome after 48 months of follow-up on their first PI-containing regimen. The P12A rare g allele was present in 12% patients with normal glucose metabolism, 11% patients with impaired glucose tolerance or impaired fasting glucose, and 35% patients with diabetes (p=0.014). The rare g allele for L162V was present in 14% of patients free of hypertriglyceridemia and in 7% patients with hypertriglyceridemia (p=0.04). The rare g allele for L162V was found in 15% of patients free of any sign of lipodystrophy and 8% with at least one sign of lipodystrophy (p=0.04) and the rare t allele for H449H was found in 14% of patients free of any sign of lipodystrophy and 23% of patients with at least one sign of lipodystrophy (p=0.05). There was no convincing association between any polymorphism of PPARα and PPARγ and each individual component of the metabolic syndrome, except for the relationship of the P12A polymorphism with diabetes. Confirmatory studies on a larger number of individuals are needed.

Hypertension in HIV-Infected Adults

“…72 The effects on lipid metabolism were also suggested by a sub-analysis of a prospective cohort study on HIV-infected individuals on PI-based regimens, which found an association between PI-related lipodystrophy and diminished levels of peroxisome proliferator activator receptor-gamma (PPAR-gamma), which regulate genes involved in lipid homeostasis and inflammation. 74 These findings were supported by an in-vitro study on human and murine adipocytes, which found that PPAR-gamma agonist exposure attenuated PI-induced RAAS activation but that PPAR antagonists increased RAAS activation. 24 The relationship between PPAR-gamma and RAAS has been extensively explored in the general population using murine models of dominant negative mutations of PPAR-gamma, which are associated with hypertension in humans.…”

Combined Metabonomic and Quantitative Real-Time PCR Analyses Reveal Systems Metabolic Changes in Jurkat T-Cells Treated with HIV-1 Tat Protein

“…Indeed, some promising therapeutic effects were observed in phase II trial of Tat vaccine. 8,9 A number of chronic metabolic abnormalities including disorders of lipid metabolism with or without lipodystrophy, 10 insulin resistance, 11 cardiometabolic syndrome, 11 altered phosphate metabolism, 12 and an increased prevalence of impaired glucose tolerance 13 are found prevalent in HIV patients with or without receiving highly active antiretroviral therapy (HAART). Although multiple risk factors have been proposed, the etiology of these metabolic abnormalities remains unclear.…”

PPARγ2 Pro12Ala polymorphism was associated with favorable cardiometabolic risk profile in HIV/HCV coinfected patients: a cross-sectional study

“…This meta-analysis suggests that, compared with rs1801282 CC genotype, carriers of rs1801282 CG/GG genotype have significant increased blood TC, and marginally significant increased blood HDL-C in healthy male subjects [ 16 ]. Moreover, there are only three articles published about PPARγ2 rs1801282 polymorphism in HIV infection [ 37 – 39 ], which did not find any association of rs1801282 polymorphism with lipodystrophy, lipid profile, and insulin sensitivity in HIV-1-infected patients treated with cART [ 37 – 39 ]. In our HIV/HCV coinfected patients, Ala variant carriers had lower values of TC, LDL-C, LDL-C/HDL-C, and AI.…”