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


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).


CONCLUSIONS
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.
UMR INSERM U1122, IGE-PCV, Université de Lorraine, Faculté de Pharmacie, Nancy, France.
Payman
P
Shahabi
Thomas
T
Cuisset
Maria G
MG
Stathopoulou
Pierre Emmanuel
PE
Morange
Charlotte
C
Grosdidier
Bernard
B
Herbeth
Gérard
G
Siest
Marie-Christine
MC
Alessi
Sophie
S
Visvikis-Siest
D000368:Aged; D002097:C-Reactive Protein / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D012907:Smoking / Q000235:genetics*; D015607:Stents; D058924:Thienopyridines / Q000009:adverse effects / Q000627:therapeutic use*; D014664:Vasodilation / Q000502:physiology
D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058924:Thienopyridines; D002097:C-Reactive Protein; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19
CRP; clopidogrel; cytochrome P450; prasugrel; smoking