ofThr 715 Pro P-selectin gene polymorphism and soluble P-selectin levels in type 2 diabetes mellitus

P-selectin is a 140-kDa integral membrane glycoprotein located in the alpha granules of platelets and the Weibel-Palade bodies of endothelial cells (1). P-selectin is a member of the selectin family that binds to a dimeric mucin (P-selectin glycoprotein ligand-1 [PSGL-1]) expressed on the surface of leukocytes. P-selectin-PSGL-1 interaction is involved in leukocyte adhesion to endothelial cells and platelets. P-selectin is expressed on the platelet or endothelial surface only upon cell activation (3). A soluble form has been identified in plasma and its level was found to increase by the cleavage of the membrane bound form from the cell surface (4). Elevated level of the soluble P-selectin (sPselectin) has been found in a number of different disorders like diabetes mellitus or ischemic cardiovascular disease (5–9). It is still a matter of debate whether sP-selectin is a causative factor in atherosclerotic or thrombotic processes or merely a marker of platelet activation (10). The P-selectin gene is located on chromosome 1q21 to 1q24 and is highly polymorphic (11). Among the 13 gene missense polymorphisms, the Thr715Pro variant has been most intensively studied (11–17). Contradictory data have been published about the association of Thr715Pro polymorphism with cardiovascular disease (CVD) (18). The presence of Pro715 allele has been shown to have a “protective” effect on myocardial infarction (MI) in two extensive studies (11, 12), but some authors reInvestigation ofThr715Pro P-selectin gene polymorphism and soluble P-selectin levels in type 2 diabetes mellitus