title: 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.
abstract: BACKGROUND
  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 and 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 wild-type controls, ten heterozygote carriers of the Thr715Pro-allele and five carriers of the rare PSGL-1 B-allele (2 A/B and 3 B/B).
  
  
  RESULTS
  CD62p-expression before application of clopidogrel and under clopidogrel treatment in Pro715-haplotype samples did not differ from that in wild-type subjects. The response to clopidogrel was similar in all subjects. Pro715-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 (121 - 230), Pro715-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 Pro715-carriers or even below this range.
  
  
  CONCLUSIONS
  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.
authors.affiliation: pharmazentrum frankfurt, Institute for Clinical Pharmacology, University Hospital Frankfurt, Frankfurt/Main, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Klinkhardt
authors.forename: I
authors.initials: I
authors.lastname: Dragutinovic
authors.forename: S
authors.initials: S
authors.lastname: Harder
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics*; D019007:P-Selectin / Q000235:genetics*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine