Association of PPARγ allelic variation, osteoprotegerin and abdominal aortic aneurysm

Abstract

Objective-We have previously demonstrated high concentrations of the glycoprotein osteoprotegerin (OPG) in biopsies of abdominal aortic aneurysm (AAA) and demonstrated that ligation of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) downregulates OPG in vitro and within a mouse model. The aims of this study were to assess the associations between circulating concentrations of OPG, polymorphisms of the gene encoding PPARγ (PPARG), AAA presence and growth.Design, patients and measurements-Two genetic polymorphisms in PPARG were assessed in 4227 men, 699 of whom had an AAA. For 631 men, who had AAAs, maximum aortic diameter was monitored by yearly ultrasound for a median of 5 years. Plasma OPG was measured in 838 men, 318 of whom had an AAA.Results-Plasma concentrations of OPG were independently associated with AAA (adjusted odds ratio 1.38, 95% CI 1.10-1.72). The PPARG c.1347C>T polymorphism was associated with plasma concentrations of OPG (beta 0.12, p<0.01). The PPARG c.34G>C polymorphism was weakly associated with AAA (adjusted odds ratio 1.28, 95% CI 1.01-1.61). PPARG c.1347C>T was associated with increased AAA growth (recessive model, p=0.03).Conclusions-Circulating concentrations of OPG are associated with AAA and with one PPARG polymorphism. PPARG polymorphisms are weakly associated with AAA presence and growth. Confirmation of these findings is required in other cohorts.

Osteoprotegerin Is Associated With Aneurysm Diameter and Proteolysis in Abdominal Aortic Aneurysm Disease

“…[18][19][20][21] Circulating OPG concentrations have also been reported to be higher in patients with AAA and positively associated with AAA progression. 4,22 In vitro experiments have suggested that OPG stimulates matrix metalloprotease (MMP) secretion from human monocytes and VSMCs, and that OPG secretion is downregulated by irbesartan. 4 These data suggest a potential role of OPG in AAA; however, currently we are aware of no studies that have reported the concentration of OPG in human AAA biopsies.…”

“…Sections were 19 stained for elastin using the elastin von Giesson method, for collagen using Picro-sirius red, 20 and for VSMCs (α-smooth muscle actin), macrophages (CD68), T-lymphocytes (CD3), B-21 lymphocytes (CD20) and plasma cells (CD138) using immunohistochemistry, as previously 22 described. 3 Immunostaining of sections with OPG was performed using the following Intraluminal thrombus measurements 16 All CTA scans were acquired on a 16-or 256-slice CT-scanner (Philips Medical Systems,…”

Association between Peroxisome Proliferator-activated Receptor Gamma Gene Polymorphisms and Atherosclerotic Diseases: A Meta-analysis of Case-control Studies

“…We next created a Galbraith plot to graphically assess the source of the heterogeneity. As a result, five studies 15,28,32,34,37) were identified as the main contributors of heterogeneity for the allelic models, two studies 15,37) were identified as the main contributors of heterogeneity for the additive and recessive models and four studies 11,28,32,37) were identified as contributors of heterogeneity for the dominant model (Fig. 7).…”

“…Among the included studies, four studies reported that the T allele protects against the risk of CAD 11,22,34,37) : one study showed that the frequency of the TT genotype is significantly higher among patients with acute myocardial infarction than in controls 15) and one study demonstrated that the TT genotype is associated with increased abdominal aortic aneurysm growth 32) . The current study provided no evidence of a significant association between the rs3856806 polymorphism and atherosclerotic diseases.…”

“…We next created a Galbraith plot to graphically assess the source of the heterogeneity. Five studies 17,20,25,32,39) were identified as the main contributors of heterogeneity for all genetic models. In addition, one study by Zafarmand et al 26) was identified as a contributor of heterogeneity for all allelic models, and two studies 18,36) were identidiseases based on ethnicity and the type of disease, significant associations were found in the Caucasian, Asian, CAD and MI subgroups.…”