Genetic determined low response to thienopyridines is associated with higher systemic inflammation in smokers

Pharmacogenomics. 2015;16(5):459-69. doi: 10.2217/pgs.15.17.

Abstract

Aim: To investigate whether the interactions of CYP2C19*2 and CYP2C19*17 with smoking are associated with the levels of P2Y12 receptor inhibition and CRP, in on-thienopyridine post-stenting patients.

Methods & results: At 1-month follow-up, the interactions of smoking and CYP2C19 polymorphisms on the vasodilator-stimulated phosphoprotein - platelet reactivity index (VASP PRI), and CRP were explored in three metabolizing groups (1128 patients) as follow: poor metabolizers (*2 carriers/*17 noncarriers); intermediate metabolizers (*2 carriers/*17 carriers or *2 noncarriers/*17 noncarriers); and ultrarapidmetabolizers (*2 allele noncarriers/*17 carriers). The interactions of metabolizing status and smoking was significant for CRP (p = 0.001) but not for VASP PRI (p = 0.734).

Conclusion: Interaction between CYP2C19 polymorphisms and smoking modifies on-treatment CRP level of post-stenting, on-thienopyridine patients. This effect seems to be independent to the level of P2Y12 receptor inhibition.

Keywords: CRP; clopidogrel; cytochrome P450; prasugrel; smoking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • C-Reactive Protein / genetics
  • Cytochrome P-450 CYP2C19 / genetics
  • Female
  • Genotype
  • Heterozygote
  • Humans
  • Inflammation / genetics*
  • Male
  • Middle Aged
  • Phosphoproteins / metabolism
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Smoking / genetics*
  • Stents
  • Thienopyridines / adverse effects
  • Thienopyridines / therapeutic use*
  • Vasodilation / physiology

Substances

  • Phosphoproteins
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Thienopyridines
  • C-Reactive Protein
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19