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.

The Impact of Clinical and Genetic Factors on Ticagrelor and Clopidogrel Antiplatelet Therapy

“…CYP2C19 is involved in metabolism of arachidonic acid derivatives (19-HETE) [40]. Arachidonic acid derivatives may act on inflammation, and it is well known that they may have a significant role in platelet aggregation [25]. Moreover, our previous studies demonstrated that CYP4F2 may affect platelet aggregation [25] and may impact stent thrombosis in patients who have undergone PCI and stent implantation [41].…”

“…Arachidonic acid derivatives may act on inflammation, and it is well known that they may have a significant role in platelet aggregation [25]. Moreover, our previous studies demonstrated that CYP4F2 may affect platelet aggregation [25] and may impact stent thrombosis in patients who have undergone PCI and stent implantation [41]. Thus, after analysis of the currently available literature, we decided to investigate the prevalence of genotypes of CYP4F2 (rs2108622, rs1558139, rs3093135 and rs2074902) in our patient population.…”

“…Transmission of light in the platelet-poor plasma was considered 100%, and platelet aggregation was expressed as % agr . Platelet aggregation after induction with ADP (final concentration, 5 μM; Chrono-Log) was determined as previously described [25].…”

Genetics of Clopidogrel Resistance: Recent Data

“…В отличие от PON-1, многообещающие перспек-тивы имеются в отношении двух других генов -CES1 [33] и CYP4F2 [34].…”

“…В доступной литературе имеется два исследования, посвященные изучению влияния полиморфизма гена CYP4F2 на активность тромбоцитов. В исследовании V. Tatarunas, et al среди 89 больных ИБС, получающих ДАТ, носители гено-типа CYP4F2 GA имели достоверно более высокий уровень агрегации тромбоцитов по сравнению с носителями генотипа GG (p=0,04) или АА (p=0,01) [34]. B другом исследовании среди 27 здоровых добро-вольцев A. Barden, et al выявлено, что агрегация тромбоцитов у добровольцев -носителей по край-ней мере 1 аллели А (CYP4F2 GA + CYP4F2 АA) -была значительно выше по сравнению с носителями генотипа CYP4F2 GG (р<0,0001) [38].…”