The Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma2 gene is associated with plasma levels of soluble RAGE (Receptor for Advanced Glycation Endproducts) and the presence of peripheral arterial disease.
OBJECTIVE
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.


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.
Research Centre on Vascular Diseases, VAS, University of Milan, Luigi Sacco Hospital, Milan, Italy.
Mariella
M
Catalano
Adriano
A
Cortelazzo
Roberto
R
Santi
Laura
L
Contino
Marta
M
Demicheli
Yusuf
Y
Yilmaz
Michele
M
Zorzetto
Ilaria
I
Campo
Niccolò
N
Lanati
Enzo
E
Emanuele
D000368:Aged; D000409:Alanine / Q000235:genetics; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016001:Confidence Intervals; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007558:Italy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D047495:PPAR gamma / Q000235:genetics*; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D012307:Risk Factors
D015415:Biomarkers; D047495:PPAR gamma; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D004247:DNA; D011392:Proline; D000409:Alanine