Soluble P-selectin levels, P-selectin polymorphisms and cardiovascular disease.
P-selectin is a member of the selectin family of cell adhesion molecules which are important in the transient attachment of leukocytes to endothelial cells and platelets. A number of polymorphisms in the gene encoding P-selectin have been identified. Objectives were to investigate the relationship of soluble P (sP)-selectin with P-selectin gene polymorphisms and coronary artery disease (CAD). Two hundred and forty-nine patients, with extent of CAD characterized by >or=50% stenosis in one or more coronary arteries, and 252 healthy controls were studied. Soluble P-selectin was significantly higher in the patients than controls after adjustment for age, sex and smoking [patients 49.8 (47.5-52.1) ng mL-1; controls 46.7 (44.5-49.1) ng mL-1, P = 0.03). There was no association of sP-selectin with myocardial infarction (MI) or presence of >or=50% stenosis. The -1817 T/C, -1969 G/A and -2123 C/G (but not the Thr715Pro) polymorphisms were in strong linkage disequilibrium. The Thr715Pro polymorphism was significantly associated with sP-selectin even after adjustment for covariates [TT 48.9 (46.9-50.0) ng mL-1; TP + PP 40.7 (38.1-43.6) ng mL-1, P < 0.0001]. A significant interaction of Thr715Pro and smoking status was identified in the determination of sP-selectin levels. There was no significant association of genotype at any of the polymorphism in relation to MI or stenosis. The Thr715Pro polymorphisms is associated with plasma sP-selectin. This association is modulated by smoking, although the underlying mechanism remains unclear.
Carter
A M
AM
Academic Unit of Molecular Vascular Medicine, Research School of Medicine, University of Leeds, Leeds, UK. medamc@medphysics.leeds.ac.uk
Anagnostopoulou
K
K
Mansfield
M W
MW
Grant
P J
PJ
D000368:Aged; D000483:Alleles; D002318:Cardiovascular Diseases / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D002448:Cell Adhesion; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism; D019040:E-Selectin / Q000097:blood / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics; D019007:P-Selectin / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking
D019040:E-Selectin; D019007:P-Selectin