ABSTRACT
OBJECTIVES: Recent evidences suggest that the activation of peroxisome proliferator-activated receptor (PPAR)-gamma2, which plays an important role in vascular homeostasis, also regulates the expression of the Receptor for Advanced Glycation End products (RAGE). In turn, low levels of soluble RAGE (sRAGE) have recently emerged as a valuable biomarker of vascular inflammation. The potential alterations in sRAGE concentrations in peripheral arterial disease (PAD), however, have not been yet investigated. The aim of the present study was to clarify whether the Pro12Ala polymorphism of the PPAR-gamma2 gene is related to plasma sRAGE levels and the presence of PAD in nondiabetic Italian individuals. DESIGN AND METHODS: A total of 201 patients with PAD and 201 PAD-free control subjects were investigated. Genotyping of the Pro12Ala polymorphism of the PPAR-gamma2 gene was performed by means of PCR-RFLPs. Plasma sRAGE levels were determined by ELISA. RESULTS: Subjects carrying at least one Ala12 allele of the PPAR-gamma2 gene had lower sRAGE levels (all p values<0.001). The prevalence rate of the Ala12 allele was significantly higher in PAD patients (14.0%) than in controls (8.0%, p=0.009). In multivariate logistic regression analysis after adjustment for potential confounders, the Ala12 allele was significantly and independently associated with the risk of PAD (OR=1.57, 95% CI=1.11-2.65, p=0.021). CONCLUSIONS: Our data indicate that the Ala12 allele of the PPAR-gamma2 gene is associated with lower levels of the soluble decoy receptor sRAGE and the presence of PAD.
Subject(s)
PPAR gamma/genetics , Peripheral Vascular Diseases/genetics , Polymorphism, Genetic , Receptors, Immunologic/blood , Aged , Alanine/genetics , Alleles , Biomarkers/blood , Case-Control Studies , Confidence Intervals , DNA/genetics , Female , Genotype , Humans , Italy , Logistic Models , Male , Middle Aged , Odds Ratio , Peripheral Vascular Diseases/blood , Polymerase Chain Reaction , Proline/genetics , Receptor for Advanced Glycation End Products , Risk FactorsABSTRACT
BACKGROUND: Plasma lipoprotein(a) [Lp(a)] levels are mainly genetically determined. The C93T polymorphism is a naturally occurring variant of the LPA gene that may influence Lp(a) concentration. The role of Lp(a) in the pathogenesis of peripheral arterial disease (PAD) has not been firmly established. METHODS: A total of 299 patients with PAD and 312 PAD-free control subjects were investigated. Genotyping of the LPA C93T polymorphism was performed by means of PCR-RFLPs. Plasma Lp(a) levels were determined by ELISA. RESULTS: Subjects carrying at least one LPA 93T allele had lower Lp(a) levels. The prevalence rate of the 93T allele was significantly higher in control subjects (19.5%) than in PAD patients (13.0%, P=0.012). In multivariate logistic regression analysis with covariates including traditional risk factors, the 93T allele was independently associated with a reduced risk of PAD (OR=0.75, 95% CI=0.51-0.95, P=0.031). CONCLUSION: The 93T allele of the LPA gene is associated with a reduced risk of PAD and low Lp(a) levels.
