P-selectin (CD62p) and P-selectin glycoprotein ligand-1 (PSGL-1) polymorphisms: Minor phenotypic differences in the formation of platelet-leukocyte aggregates and response to clopidogrel

Introduction: Formation of platelet-leukocyte aggregates (PLA) via the CD62p-ligand PSGL-1 represents an important mechanism by which leukocytes contribute to thrombotic and inflammatory events. Deficient variants (namely the Thr715Pro-SNP for CD62p and a VNTR-polymorphism for PSGL-1) might affect PLA formation an probably the response to clopidogrel (which is known to reduce PLA-formation). Methods: CD62p-expression, PLA-formation and the up-regulation of CD11b before (V1) and 24 hours after (V2) a loading dose of clopidogrel 225 mg were investigated in ten wildtype controls, ten heterozygote carriers of the Thr715Pro-allele and five carriers of the rare PSGL-1B-allele (2 A/B and 3 B/B). Results: CD62p-expression before application of clopidogrel and under clopidogrel treatment in Pro(715)-haplotype samples did not differ from that in wild-type subjects. The response to clopidogrel was similar in all subjects. Pro(715)-carriers exhibited a significantly lower percentage of monocytes with platelets attached prior to clopidogrel treatment (ADP: median 22 (1st - 3rd quartile 20 - 23), TRAP: 27 (25 - 38)) compared to the wild-type (ADP: 37 (31 - 44), TRAP: 55 (37 - 63)). These differences were not present under clopidogrel, and CD11b-expression was significantly reduced in both groups (controls: median 150 (quartile range 121 - 230) to 113 (12 1 - 230), Pro(715)-carriers: 147 (139 - 221) to 126 (109 - 170); all values refer to mean fluorescence intensity). Statistical analysis was not done in the case of PSGL-1 B-allele carriers, but PLA-formation before and under clopidogrel was always at the bottom end of the range seen in the control group and the Pro(715)-carriers or even below this range. Conclusion: Minor phenotypic differences in the CD62p-PSGL-1 axis could be demonstrated in this study. Carriers of these polymorphisms showed a full response to clopidogrel comparable to that in control subjects.