title: The role of clinical parameters and of CYP2C19 G681 and CYP4F2 G1347A polymorphisms on platelet reactivity during dual antiplatelet therapy.
abstract: Dual antiplatelet therapy with aspirin and clopidogrel is used to lower the risk of arterial thrombosis. However, this strategy is not always successful owing to high interindividual variability in response to antiplatelet therapy. To evaluate an impact of CYP2C19 G681A and CYP4F2 G1347A polymorphisms and clinical factors on dual antiplatelet effect of clopidogrel and aspirin. Totally 89 patients who continued dual aspirin and clopidogrel antiplatelet therapy for at least of 14 days were included into the further study. Test for platelet aggregation was performed according to the classical Born method. Genotyping of CYP2C19*2 and CYP2C19*3 and CYP4F2*3 was done by using commercial probes from Applied Biosystems (UK). Patient age, weight and body weight index did not correlate significantly with platelet aggregation level both induced by ADP and epinephrine (P > 0.05). Serum concentration of creatinine, diabetes, angiotensin II receptor blockers, B-blockers, statin or omeprazole use had no significant effect on platelet aggregation. The users of angiotensin-converting enzyme inhibitors had lower platelet aggregation levels with epinephrine vs. nonusers: 28.80 ± 13.25 vs. 51.15 ± 23.50, P < 0.03, respectively. Platelet aggregation with ADP was higher in CYP2C19*1*2 genotype carriers than in CYP2C19*1*1 carriers (P = 0.01). Platelet aggregation with epinephrine was higher in CYP4F2 GA genotype carriers than in GG (P = 0.04) or AA (P = 0.01) carriers. Our study confirms that CYP2C19 G681A genotype has an impact on antiplatelet effect of clopidogrel. The novelty is that the platelet aggregation after induction with epinephrine is influenced by CYP4F2 G1347A genotype.
authors.affiliation: aInstitute of Cardiology bDepartment of Internal Diseases cDepartment of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Vacis
authors.initials: V
authors.lastname: Tatarunas
authors.forename: Laima
authors.initials: L
authors.lastname: Jankauskiene
authors.forename: Nora
authors.initials: N
authors.lastname: Kupstyte
authors.forename: Vilius
authors.initials: V
authors.lastname: Skipskis
authors.forename: Olivija
authors.initials: O
authors.lastname: Gustiene
authors.forename: Pranas
authors.initials: P
authors.lastname: Grybauskas
authors.forename: Vaiva
authors.initials: V
authors.lastname: Lesauskaite
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000097:blood / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000097:blood / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D020641:Polymorphism, Single Nucleotide; D013927:Thrombosis / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D003577:Cytochrome P-450 Enzyme System; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; D013988:Ticlopidine; D001241:Aspirin; D004837:Epinephrine