Association between PPARGC1A gene polymorphisms and coronary artery disease in a Chinese population.
ABSTRACT Peroxisome proliferrator-activated receptor gamma coactivator-1alpha (PGC-1alpha; PPARGC1A) is a coactivator of the nuclear hormone receptor family that participates in the transcriptional programme of lipid metabolism and oxidative stress implicated in atherogenesis. Therefore, in the present study, we investigated PPARGC1A polymorphisms in the prevalence of coronary artery disease (CAD). A case-control study comprising 342 patients with CAD and 334 controls was performed in a Chinese population. Two single nucleotide polymorphisms (Gly482Ser and Thr394Thr) in the PPARGC1A gene were genotyped and compared using the polymerase chain reaction-restriction fragment length polymorphism method. The XA (GA + AA) genotype of Gly482Ser displayed a higher frequency in CAD patients than that in control subjects (P = 0.019; adjusted odds ratio = 1.53; 95% confidence interval 1.06-2.20). No significant difference in Thr394Thr genotype distribution or in Gly482Ser-Thr394Thr haplotype combinations was found between CAD patients and controls. Furthermore, we found that the significantly increased risk of CAD associated with the XA genotypes of Gly482Ser was more evident among subjects who were younger than 64 years of age, female, overweight and with hypertension. The results indicate that the PPARGC1A Gly482Ser polymorphism may contribute to the risk of CAD in the Chinese population investigated.
Article: ApoE-/- PGC-1α-/- mice display reduced IL-18 levels and do not develop enhanced atherosclerosis.[show abstract] [hide abstract]
ABSTRACT: Atherosclerosis is a chronic inflammatory disease that evolves from the interaction of activated endothelial cells, macrophages, lymphocytes and modified lipoproteins (LDLs). In the last years many molecules with crucial metabolic functions have been shown to prevent important steps in the progression of atherogenesis, including peroxisome proliferator activated receptors (PPARs) and the class III histone deacetylase (HDAC) SIRT1. The PPARγ coactivator 1 alpha (Ppargc1a or PGC-1α) was identified as an important transcriptional cofactor of PPARγ and is activated by SIRT1. The aim of this study was to analyze total PGC-1α deficiency in an atherosclerotic mouse model. To investigate if total PGC-1α deficiency affects atherosclerosis, we compared ApoE(-/-) PGC-1α(-/-) and ApoE(-/-) PGC-1α(+/+) mice kept on a high cholesterol diet. Despite having more macrophages and a higher ICAM-1 expression in plaques, ApoE(-/-) PGC-1α(-/-) did not display more or larger atherosclerotic plaques than their ApoE(-/-) PGC-1α(+/+) littermates. In line with the previously published phenotype of PGC-1α(-/-) mice, ApoE(-/-) PGC-1α(-/-) mice had marked reduced body, liver and epididymal white adipose tissue (WAT) weight. VLDL/LDL-cholesterol and triglyceride contents were also reduced. Aortic expression of PPARα and PPARγ, two crucial regulators for adipocyte differentiation and glucose and lipid metabolism, as well as the expression of some PPAR target genes was significantly reduced in ApoE(-/-) PGC-1α(-/-) mice. Importantly, the epididymal WAT and aortic expression of IL-18 and IL-18 plasma levels, a pro-atherosclerotic cytokine, was markedly reduced in ApoE(-/-) PGC-1α(-/-) mice. ApoE(-/-) PGC-1α(-/-) mice, similar as PGC-1α(-/-) mice exhibit markedly reduced total body and visceral fat weight. Since inflammation of visceral fat is a crucial trigger of atherogenesis, decreased visceral fat in PGC-1α-deficient mice may explain why these mice do not develop enhanced atherosclerosis.PLoS ONE 01/2010; 5(10):e13539. · 4.09 Impact Factor