The P-selectin gene Pro715 allele and low levels of soluble P-selectin are associated with reduced P2Y12 adenosine diphosphate receptor reactivity in clopidogrel-treated patients

Atherosclerosis. 2011 Jul;217(1):135-8. doi: 10.1016/j.atherosclerosis.2011.03.029. Epub 2011 Mar 31.

Abstract

Objective: To investigate the interrelation between the P-selectin gene (SELP) Pro715 allele, P2Y12 adenosine diphosphate (ADP) receptor reactivity and levels of soluble P-selectin (sP-selectin) in clopidogrel treated patients.

Methods: The Pro715 allele within SELP was tested by allele specific PCR, sP-selectin was determined by ELISA, and P2Y12 receptor reactivity was analyzed by the VASP assay in 156 patients after angioplasty and stenting.

Results: Carriers of the SELP Pro715 allele had significantly lower levels of sP-selectin and P2Y12 receptor reactivity, and high on-treatment residual P2Y12 receptor reactivity (HRPR) was significantly less frequent compared to non-carriers (both p<0.05). Further, patients within the lowest quartile of sP-selectin had significantly lower reactivity values and also less often HRPR compared to patients with higher sP-selectin (both p<0.01).

Conclusion: The SELP Pro715 allele is linked to low levels of sP-selectin, and both are associated with decreased P2Y12 ADP receptor reactivity in patients on clopidogrel therapy.

MeSH terms

  • Adult
  • Alleles
  • Angioplasty / methods
  • Clopidogrel
  • Female
  • Humans
  • Male
  • Middle Aged
  • P-Selectin / blood*
  • P-Selectin / genetics*
  • Platelet Aggregation Inhibitors / pharmacology
  • Polymorphism, Genetic
  • Proline / genetics
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / pharmacology
  • Receptors, Purinergic P2Y12 / genetics*
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / pharmacology

Substances

  • P-Selectin
  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y12
  • Proline
  • Clopidogrel
  • Ticlopidine