Soluble P-selectin levels, P-selectin polymorphisms and cardiovascular disease

Abstract

Summary. 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 ≥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 ≥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.

High Concentrations of Soluble P-Selectin Are Associated with Risk of Venous Thromboembolism and the P-Selectin Thr715 Variant

“…1B). Carriers of the SELP Pro715 allele had significantly lower sP-selectin concentrations (Table 3), a finding that is concordant with every study that has investigated the association of sP-selectin concentration with the SELP Thr715Pro allele (25)(26)(27). We assume that the ELISA used in our study is equally sensitive to both variants (Thr715 and Pro715).…”

“…One such variant, a single nucleotide polymorphism that produces the amino acid substitution Thr715Pro, has consistently been associated with lower sP-selectin concentrations in plasma (25)(26)(27), but the data on the effect of this variant on myocardial infarction and stroke are conflicting (25)(26)(27)(28)(29).…”

An Application of Logistic Regression and Multifactor Dimensionality Reduction Analyses for Detecting Genotype-Phenotype Interactions Associated with Developing of Atherosclerosis in Bulgarian Cohort

“…The results from MDR also showed several genetic interactions that were significant after permutation testing. Our findings appear to be of importance and relevant because they implicated involvement of genes, which have been shown previously to be connected with development of atherosclerosis (10,11,14,15,27,30,46). The use of MDR closely reassembles the complex nature and multifactorial base of the disease by evaluating multiple SNPs in an unbiased way.…”

“…It was studied that cell adhesion molecules like Selectin P are important for the attachment of leukocytes to endothelial cells and platelets (11). Several polymorphisms in SELP gene were investigated for association with CVD (18).…”

“…The primers and the conditions for the PCR reactions and restriction enzymes are previously described (2,7,11,13,14,16,23,26,30,41,45,46).…”