PPARγ gene C161T substitution alters lipid profile in Chinese patients with coronary artery disease and type 2 diabetes mellitus

Abstract

BackgroundPeroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor, which regulates gene expression of the key proteins involved in lipid metabolism, vascular inflammation, and proliferation. PPARγ may contribute to attenuating atherogenesis and postangioplasty restenosis. PPARγ C161→T substitution is associated with a reduced risk of coronary artery disease (CAD). Whether or not the gene substitution alters the risk of CAD in type 2 diabetes mellitus (T2DM) patients remains unclear.MethodsA total of 556 unrelated subjects from a Chinese Han population, including 89 healthy subjects, 78 CAD patients, 86 T2DM patients, and 303 CAD combined with T2DM patients, were recruited to enroll in this study. PPARγC161→T gene polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphisms. Plasma levels of lipoproteins, apolipoproteins, glucose, and insulin were measured by ELISA or radioimmunoassay (RIA). The coronary artery lesions were evaluated by coronary angiography.ResultsThe frequency of the 161T allele in CAD, T2DM, and CAD combined with T2DM patients was similar to that observed in the healthy control group. However, in CAD combined with T2DM patients, the group with angiographically documented moderate stenoses had a higher frequency of the 161T allele in comparison to the group with severe stenoses (P < 0.05). Moreover, in CAD with T2DM patients, the triglyceride levels and apoB in CC homozygote carriers were significantly higher than those in "T" allele carriers.ConclusionsPPARγC161→T genotypes weren't significantly associated with the risk of CAD, but were markedly correlated with severity of disease vessels in patients with CAD and T2DM. Furthermore, PPARγC161→T substitution was associated with an altered adipose, but not glucose metabolism. These results indicate that the PPARγ C161→T polymorphism may reduce the risk of severe atherogenesis by modulation of adipose metabolism, especially triglycerides and apoB, in Chinese patients with CAD and T2DM.

Impact of the C1431T Polymorphism of the Peroxisome Proliferator Activated Receptor-Gamma (PPAR-&#947;) Gene on Fasted Serum Lipid Levels in Patients with Coronary Artery Disease

“…In agreement with these observations, several recent studies have shown the effects of the C161T polymorphism on lipid profile and apolipoprotein ratios [19,20,29,35]. Additionally, several other studies showed the associations of other polymorphisms of PPAR-γ with lipid parameters, such as TG, TC, LDL and HDL [36,37,38,39,40]. In particular, Zhou and colleagues showed that this polymorphism was associated with a higher HDL-C level and a lower blood glucose level in CAD patients [15,39].…”

“…Zhou et al showed that this polymorphism was associated with decreased risk of CAD in Chinese Han population [15]. On the other hand, several other studies have reported inconsistent data [5,14,28,29]. In particular, Vats and colleagues showed the lack of association between the allelic and genotypic frequencies of cases and controls [14].…”

“…Additionally, several other studies showed the associations of other polymorphisms of PPAR-γ with lipid parameters, such as TG, TC, LDL and HDL [36,37,38,39,40]. In particular, Zhou and colleagues showed that this polymorphism was associated with a higher HDL-C level and a lower blood glucose level in CAD patients [15,39]. …”

“…There is a growing body of evidence showing an association between the PPAR-γ polymorphism with CAD [15,28,29]. Our recent study found associations between this polymorphism and their haplotypes with susceptibility to metabolic syndrome as an increased risk factor of CAD [17,30].…”

Effects of the PPARG Gene Polymorphisms on Markers of Obesity and the Metabolic Syndrome in Bosnian Subjects

“…Nevertheless, positive effects of this SNP on the metabolic phenotype have been demonstrated earlier. It has been associated with a favorable lipid profile (24,33,53), and reduced risk of coronary artery disease (54) and severe atherogenesis (24).…”