A novel functional polymorphism in the PECAM-1 gene (53G>A) is associated with progression of atherosclerosis in the LOCAT and REGRESS studies.

Abstract

A 53G>A polymorphism identified in the 5' untranslated region (5'UTR) of the platelet endothelial cell adhesion molecule-1 (PECAM-1) gene alters a putative shear stress responsive element (SSRE). PECAM-1 was shown to be responsive to shear stress and transient transfection of human umbilical vein endothelial cell (HUVECs) with two luciferase reporter constructs driven by the PECAM-1 promoter and 5'UTR showed a response of the 53G allele, not the 53A allele, to shear stress. Association between the 53G>A, and the previously published L125V polymorphism, and coronary atherosclerosis was examined in two angiographic studies. The frequencies of the rare alleles of the 53G>A and L125V polymorphisms were 0.01 and 0.49, respectively, in the Lopid Coronary Angiography Trial (LOCAT) study and 0.02 and 0.49, respectively, in the Regression Growth Evaluation Statin Study (REGRESS) study. Compared with 53G homozygotes, carriers of the 53A allele showed less focal progression of disease in the LOCAT study and a similar trend in the diffuse progression of disease in the REGRESS study, whereas no association between L125V and coronary atherosclerosis was observed in either study. These data demonstrate that the PECAM-1 gene is responsive to shear stress in vitro and that decreased PECAM-1 gene expression in 53A carriers may influence reduced progression of vessel stenosis in patients with coronary artery disease.

• Authors: Mohamed A Elrayess, Karen E Webb, David M Flavell, Mikko Syvänne, Marja-Riitta Taskinen, M Heikki Frick, Markku S Nieminen, Y Antero Kesäniemi, Amos Pasternack, J Wouter Jukema, John J P Kastelein, Aeilko H Zwinderman, Steve E Humphries
• Journal: Atherosclerosis (Atherosclerosis) Vol. 168 Issue 1 Pg. 131-8 (May 2003) ISSN: 0021-9150 [Print] Ireland
• PMID: 12732396 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Complementary
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Platelet Endothelial Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• Glyceraldehyde-3-Phosphate Dehydrogenases

Topics

• Aged
• Alleles
• Computer Systems
• Coronary Angiography
• Coronary Artery Disease (drug therapy, genetics)
• DNA, Complementary (genetics)
• Disease Progression
• Endothelium, Vascular (chemistry, cytology)
• Finland
• Follow-Up Studies
• Gene Frequency (genetics)
• Gene Order (genetics)
• Genetic Predisposition to Disease (genetics)
• Genotype
• Glyceraldehyde-3-Phosphate Dehydrogenases (genetics)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Intercellular Adhesion Molecule-1 (genetics)
• Male
• Middle Aged
• Multivariate Analysis
• Platelet Endothelial Cell Adhesion Molecule-1 (genetics)
• Polymerase Chain Reaction
• Polymorphism, Genetic (genetics)
• Promoter Regions, Genetic (genetics)
• Statistics as Topic
• Stress, Mechanical
• Transfection
• Umbilical Veins (chemistry, cytology)