Coexisting Polymorphisms of P2Y12 and CYP2C19 Genes as a Risk Factor for Persistent Platelet Activation With Clopidogrel

Małek, Łukasz A.; Kisiel, Bartłomiej; Śpiewak, Mateusz; Grabowski, Marcin; Filipiak‬, Krzysztof J.; Kostrzewa, Grażyna; Huczek, Zenon; Płoski, Rafał; Opolski, Grzegorz

doi:10.1253/circj.72.1165

Cited by 82 publications

(58 citation statements)

References 30 publications

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“…Few studies done on different population concluded that the carriers with H2 alleles have higher propensity for CAD with maximal platelet aggregation in response to ADP (Fontana et al 2003a) (Bura et al 2006) (Cavallari et al 2007). However, on the contrary, similar studies concluded that the gene sequence variation in P2Y12 did not contribute to the risk of development of CAD in Caucasian (Smith et al 2006) (Lev et al 2007) (Zee et al 2008) (Malek et al 2008), in French (Cuisset et al 2007), in Brazilian (Schettert et al 2006), in Mexican (Isordia-Salas et al 2012, in Italian (Giusti et al 2007), and Korean population (Lee et al 2011) (Jang et al 2012). Thus, the reasons for such conflicting results may be that a combination of hemostatic gene polymorphisms may be implicated in development of CAD rather than P2Y12 as a single entity (Martinelli et al 2008) (Tang et al 2013).…”

Section: Discussionmentioning

confidence: 94%

Frequency of single nucleotide platelet receptor gene polymorphism (P2Y12-i744T>C) in coronary artery disease patients among Tamilian population

et al. 2017

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Several factors contribute to the development of coronary artery disease (CAD). Adenosine diphosphate (ADP) activated P2Y12 receptor also plays a key role in platelet activation and aggregation. It has been found that common variation in the P2Y12 gene was associated with increased platelet aggregation resulting in adverse cardiovascular outcomes. Thus, polymorphisms in the ADP receptor P2Y12 may contribute to the development of CAD. This study aims to determine the frequency distribution of platelet receptor polymorphism P2Y12 (i744T>C) in Tamilian population and to predict its possible role in CAD. Three hundred seventyone subjects were recruited comprising of 221 healthy volunteers and 150 patients with CAD belonging to either sex, aged 18-60 years of Tamilian origin. Genomic DNA was extracted using phenol-chloroform method. Genotyping was done by PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism). The C allele frequency of P2Y12 polymorphism in controls and cases was 8.4% and 17.7%, respectively. The TT, TC, and CC genotype frequencies in controls and cases were 83.7%, 15.8%, 0.5% and 66.7%, 31.3%, 2%, respectively. The genotype frequencies were in HardyWeinberg equilibrium. There was a significant association (p < 0.05) between the mutant genotypes of P2Y12 (i744T>C) polymorphism and risk of CAD. The odds ratio was found to be 2.6. The variant allele frequency of P2Y12-i744T>C was significantly different from other populations. There was a significant association between the mutant genotypes of P2Y12 (i744T>C) polymorphism and risk of developing CAD. Thus, the present study will emphasize on the relevance of pharmacogenetic testing of P2Y12 (i744T>C) receptor gene polymorphism in CAD patients.

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Section: Discussionmentioning

confidence: 94%

Frequency of single nucleotide platelet receptor gene polymorphism (P2Y12-i744T>C) in coronary artery disease patients among Tamilian population

et al. 2017

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“…Single nucleotide polymorphisms (SNPs) in Cyp2C19 have been suggested as causes of resistance. [22][23][24] There is an interethnic variability in the rate of the Cyp2C19 SNPs that cause Cyp2C19 to be non-functional and approximately 20% of Japanese people have been reported to possess little Cyp2C19 activity in contrast to only 2.5% of Westerners. 25 Therefore, a genetic defect in Cyp2C19 might have a great influence on clopidogrel effectiveness in the Japanese.…”

Section: Discussionmentioning

confidence: 99%

“…ASA was administered at a daily dose of 81-100 mg. Blood samples were collected at enrolment, and at 4 (3-5) h, 24 (22)(23)(24)(25)(26) h and 48 (46-50) h after the loading dose ( Table 1). The 24-h sampling was performed before the daily 75 mg clopidogrel intake, whereas the 48-h sampling was afterward.…”

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confidence: 99%

Clopidogrel Resistance in Japanese Patients Scheduled forPercutaneous Coronary Intervention

Hoshino

Horiuchi

Tada

et al. 2009

Circ J

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Background Dual antiplatelet therapy with acetylsalicylic acid (ASA) and a P2Y12 ADP-receptor blocker is standard for prevention of coronary stent thrombosis. Clopidogrel, a 2 nd -generation P2Y12 blocker, has recently become available in Japan and this study aimed to evaluate its antiplatelet effects in Japanese patients. Methods and ResultsThirty Japanese patients scheduled for elective coronary stent implantation were enrolled. Under low-dose ASA therapy, 300 mg clopidogrel was loaded on the 1 st day and a daily 75-mg dose was administered on the following days. Assessed by optical aggregometer, rapid inhibition occurred at 4 h, when the inhibition of platelet aggregation rate (IPA) was 16.4±12.8% using 5 μmol/L ADP as the stimulus. The antiplatelet efficacy of clopidogrel was reasonably constant in each patient throughout the study period, although there was a broad inter-individual variation. At 48 h after clopidogrel loading, the ratios of responders (IPA ≥30%), hypo-responders (10%≤IPA<30%), and non-responders (IPA <10%) were 36%, 50%, and 14%, respectively. Conclusions The antiplatelet effectiveness of clopidogrel appeared individual-specific with wide inter-individual variation. The rate of clopidogrel non-responders was 14% among the examined Japanese patients. (Circ J 2009; 73: 336 -342)

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“…Second, this study did not have a placebo arm; therefore, we cannot definitively conclude that use of either omeprazole or rabeprazole attenuates platelet function because of the disappearance of the superior effect of the LD of clopidogrel, which has been used in approximately 20% of both cohorts. Third, genetic polymorphism of CYP2C19 3,24,25 and P2Y12 receptor 26 have recently been shown to modulate clopidogrel's action. Because we did not perform genetic testing for CYP2C19, the effect of CYP2C19 genetic polymorphism on our study results was unknown.…”

Section: Omeprazole Vs Rabeprazole For Clopidogrel Efficacymentioning

confidence: 99%

Comparison Between the Effect of Omeprazole and Rabeprazole on the Antiplatelet Action of Clopidogrel

Siriswangvat

Sansanayudh

Nathisuwan

et al. 2010

Circ J

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Coexisting Polymorphisms of P2Y12 and CYP2C19 Genes as a Risk Factor for Persistent Platelet Activation With Clopidogrel

Cited by 82 publications

References 30 publications

Frequency of single nucleotide platelet receptor gene polymorphism (P2Y12-i744T>C) in coronary artery disease patients among Tamilian population

Frequency of single nucleotide platelet receptor gene polymorphism (P2Y12-i744T>C) in coronary artery disease patients among Tamilian population

Clopidogrel Resistance in Japanese Patients Scheduled forPercutaneous Coronary Intervention

Comparison Between the Effect of Omeprazole and Rabeprazole on the Antiplatelet Action of Clopidogrel

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