Carter A M, Anagnostopoulou K, Mansfield M W, Grant P J
Academic Unit of Molecular Vascular Medicine, Research School of Medicine, University of Leeds, Leeds, UK.
J Thromb Haemost. 2003 Aug;1(8):1718-23. doi: 10.1046/j.1538-7836.2003.00312.x.
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.
P-选择素是细胞黏附分子选择素家族的成员，在白细胞与内皮细胞和血小板的短暂黏附中起重要作用。已在编码P-选择素的基因中鉴定出许多多态性。目的是研究可溶性P（sP）-选择素与P-选择素基因多态性及冠状动脉疾病（CAD）之间的关系。对249例CAD患者（其CAD程度以一条或多条冠状动脉狭窄≥50%为特征）和252例健康对照者进行了研究。在调整年龄、性别和吸烟因素后，患者的可溶性P-选择素水平显著高于对照者[患者49.8（47.5 - 52.1）ng/mL；对照者46.7（44.5 - 49.1）ng/mL，P = 0.03]。sP-选择素与心肌梗死（MI）或狭窄≥50%的存在无关。-1817 T/C、-1969 G/A和-2123 C/G（但Thr715Pro多态性除外）多态性处于强连锁不平衡状态。即使在调整协变量后，Thr715Pro多态性仍与sP-选择素显著相关[TT型48.9（46.9 - 50.0）ng/mL；TP + PP型40.7（38.1 - 43.6）ng/mL，P < 0.0001]。在sP-选择素水平的测定中，发现Thr715Pro多态性与吸烟状态之间存在显著交互作用。任何多态性的基因型与MI或狭窄均无显著关联。Thr715Pro多态性与血浆sP-选择素相关。这种关联受吸烟调节，但其潜在机制尚不清楚。
