Polymorphisms in the P-selectin (CD62P) and P-selectin glycoprotein ligand-1 (PSGL-1) genes and coronary heart disease

Bugert, Peter; Vosberg, Marion; Entelmann, Mathias; Jahn, Jürgen; Katus, Hugo A.; Klüter, Harald

doi:10.1515/cclm.2004.202

Cited by 34 publications

(51 citation statements)

References 26 publications

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“…The association did not survive correction for multiple testing. Nevertheless, the association of rs2228315 with coronary artery disease and stroke has been shown by two studies [14,15]. Third, regression analysis did not show that stroke was correlated with known vascular risk factors but also revealed PLA as independently correlated with stroke.…”

Section: Discussionmentioning

confidence: 90%

Determinants of Platelet-Leukocyte Aggregation and Platelet Activation in Stroke

Schmalbach¹,

Stepanow²,

Jochens

et al. 2015

Cerebrovasc Dis

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Background: Platelet-leukocyte aggregation (PLA) and platelet activation are found to be on the higher side in ischemic stroke patients. The correlation of PLA with clinical features has not been intensively investigated and the influence of genetic factors on PLA is still unexplored. The interaction of platelets with leukocytes is mainly determined by the proteins encoded by six genes: P-Selectin (SELP encodes CD62P) on the thrombocyte binding to P-Selectin-Glycoprotein-Ligand-1 (PSGL1) on the leukocyte, intracellular-adhesion-molecule 2 (ICAM2) interacting with Integrin alpha M (ITGAM) and Glycoprotein 1b-alpha (GP1BA) binding to Integrin alpha L (ITGAL). Methods: Seventy-nine patients with acute ischemic stroke and 151 controls without vascular disease from a single German center were enrolled. A neurologist and a neuroradiologist ascertained clinical and radiological features. PLA and platelet activation were analyzed using flow cytometry with various antibodies. Coding as well as tagging SNPs in six genes determining PLA were genotyped. Three groups of parameters were correlated with each other: (i) clinical and radiological parameters, (ii) laboratory parameters, (iii) genetic parameters. For the comparisons, robust nonparametric statistical tests were applicable. Results: PLA and platelet activation were higher in ischemic stroke patients compared to controls. Both, anticoagulant and antiplatelet treatment in the patient group affected platelet activation but not PLA. PLA correlated weakly with measures of stroke severity but not with thrombus length or stroke etiology. The association of SNP rs2228315 in the P-Selectin Glycoprotein Ligand-1-gene (PSGL1) with ischemic stroke and platelet activation was significant before correction for multiple testing while a trend was observed for the association with PLA. Regression analysis revealed that (i) platelet activation was an independent determinant of stroke, (ii) that PLA correlated with stroke, sex, age and platelet activation and (iii) that platelet activation correlated only with stroke. None of the SNPs survived in the regression analysis for stroke, PLA or platelet activation as dependent variables. Conclusions: The most important result of our study is that PLA and platelet activation are independent of other vascular risk factors correlated with stroke in our sample. In addition, we identified the missense SNP rs2228315 in the PSGL1-gene as a candidate polymorphism for ischemic stroke-related PLA. Association between this SNP and stroke as well as coronary artery disease has also been shown by two other studies.

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Section: Discussionmentioning

confidence: 90%

Determinants of Platelet-Leukocyte Aggregation and Platelet Activation in Stroke

Schmalbach¹,

Stepanow²,

Jochens

et al. 2015

Cerebrovasc Dis

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“…A new polymorphism (V168M) in exon 5 of P-selectin gene has also been described. Further analysis should be performed to elucidate its functional role [64].…”

Section: Pharmacogenetics Of P-selectin and Psgl-1 P-selectin Or Cd62pmentioning

confidence: 99%

The Dialogue Between Endothelial Cells and Monocytes/Macrophages in Vascular Syndromes

Martin¹,

Collot-Teixeira²,

McGregor³

et al. 2007

CPD

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The aim of this chapter is to present and identify potential pharmacological targets in endothelial cell-monocyte interactions leading to vascular syndrome and involving inflammation, coagulation, vascular remodelling and thrombosis. Increasing evidence is indicating that endothelial cells play a key role in atherothombosis by their capacity to attract, bind and allow the extravasation of monocytes to sites of inflammation. Surface expression and/or activation of constituent cell adhesion molecules (for e.g. P-selectin, E-selectin, ICAM-1, and VCAM-1) on endothelial cells together with chemokines such as CXCL8 (IL-8), Platelet-activating factor (PAF), CCL2 and CCL5 (Table 1) allow the rolling, adhesion and extravasation of monocytes. This review focuses on pharmacological targets implicated in endothelial cells interactions with monocytes/macrophages in vascular disease states and on cutting edge genomic tools for the identification and characterization of such targets.

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“…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).…”

mentioning

confidence: 99%

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

Ay¹,

Jungbauer²,

Sailer³

et al. 2007

Clinical Chemistry

116

109

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Background:The cell adhesion molecule P-selectin has an important role in the pathophysiology of thrombosis. The effect on venous thromboembolism (VTE) of increased circulating concentrations of soluble P-selectin (sP-selectin) and their association with the P-selectin variant Thr715Pro is still uncertain. Methods: This study was a case-control study of 116 patients with confirmed recurrent VTE and at least 1 event of unprovoked deep venous thrombosis or pulmonary embolism, and 129 age-and sex-matched healthy individuals. We measured sP-selectin by ELISA and P-selectin gene (SELP) variation by genotyping and sampled blood after a mean interval of 2.55 years after the most recent VTE event. Results: The mean (SD) sP-selectin concentration was higher in patients than in controls: 47.3 (15.0) g/L vs 36.8 (11.0) g/L, P <0.001. The unadjusted odds ratio (OR) for sP-selectin >55.1 g/L, representing the 95th percentile for controls, was 8.5 (95% CI, 3.7-23.3; P <0.001) and increased after adjustment for factor V Leiden, the prothrombin G20210A variant, increased factor VIII, and hyperhomocysteinemia (OR, 10.6; 95% CI, 4.1-31.2; P <0.001). Pro715 carriers were more prevalent among controls than patients (21.7% vs 14.7%).

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Polymorphisms in the P-selectin (CD62P) and P-selectin glycoprotein ligand-1 (PSGL-1) genes and coronary heart disease

Cited by 34 publications

References 26 publications

Determinants of Platelet-Leukocyte Aggregation and Platelet Activation in Stroke

Determinants of Platelet-Leukocyte Aggregation and Platelet Activation in Stroke

The Dialogue Between Endothelial Cells and Monocytes/Macrophages in Vascular Syndromes

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

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