Pharmacogenetics of Antithrombotic Drugs: Status Update on the Problem

Кропачева, Е. С.

doi:10.21518/2307-1109-2018-2-115-129

Aterotromboz

2018

DOI: 10.21518/2307-1109-2018-2-115-129

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Pharmacogenetics of Antithrombotic Drugs: Status Update on the Problem

Е. С. Кропачева

Abstract: The review deals with the main trials devoted to the study of genetic markers of individual variability in drug response to antithrombotic agents. The first part describes the studies of the genes encoding the platelet receptor subunits studied in the association of the possible insufficient effect of acetylsalicylic acid, and transporter proteins and allelic variants with reduced CYP450 functional activity, which are associated with insufficient effect on clopidogrel therapy. The second part considers polymor… Show more

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Cited by 3 publications

References 79 publications

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Association of polymorphic variants of CYP2C19, P2RY12, ITGB3, ITGA2 and eNOS3 genes with high residual platelet reactivity while taking clopidogrel and acetylsalicylic acid at different terms of myocardial infarction

Pronko

Snezhitskiy

Stepuro

et al. 2023

Racionalʹnaâ farmakoterapiâ v kardiologii

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Aim. Study of the association of polymorphic variants of CYP2C19 (G681A), P2RY12 (H1/H2), ITGB3 (T1565C), ITGA2 (C807T), eNOS3 (T786C) genes with high residual platelet reactivity (HRPR) to clopidogrel and acetylsalicylic acid (ASA) at different terms of myocardial infarction (MI).Material and methods. The study included 400 patients with MI aged 31-74 years, 317 (79,3%) men and 83 (20,7%) women. Platelet aggregation performed on days 1-2, 12-14 and 28-30 of MI, and genotyping by the polymerase chain reaction were analyzed using the STATISTICA 10.0 program.Results. Differences were found in ADP-test 1-3 depending on the CYP2C19 (G681A) polymorphism, ADP-test 1 depending on the P2RY12 (H1/H2) polymorphism, ADP-test 2 depending on the ITGB3 (T1565C) polymorphism, ASPI-test 1 depending on the eNOS (T786C) polymorphism. The risk of HRPR to clopidogrel is higher in 681A CYP2C19 allele carriers compared to the G681 carriers throughout the entire observation period: initially odds ratio (OR) of 1,8 (1,14-2,88), p=0,012, on days 12-14 of MI, OR of 1,7 (1,08-2,68), p=0,023 and on days 28-30 of MI, OR of 2,3 (1,42-3,81), p=0,0008. The risk of HRPR to clopidogrel is higher in AA CYP2C19 genotype carriers compared to GG genotype carriers, on days 1-2 of MI (OR 6,5 (1,16-36,4), p=0,033), on days 28-30 of MI (OR 7,8 (1,26-48,0), p=0,027). The risk of HRPR to clopidogrel on days 1-2 of MI is higher in H2 P2RY12 locus carriers compared to H1 locus carriers (OR 1,5 (1,02-2,22), p=0,039). The risk of HRPR to ASA on days 1-2 of MI is higher in the 786C eNOS3 allele carriers compared to T786 allele carriers (OR 1,4 (1,02-1,96), p=0,036). Carriers of haplotypes of minor alleles of CYP2C19 + ITGA2 + P2RY12 + eNOS genes (OR 3,9 (1,13-13,65), p=0,032) and CYP2C19 + ITGA2 + eNOS genes (OR 5,1 (1,7214,96), p=0,0032) have higher risk of HRPR to dual antiplatelet therapy (DAPT) on days 28-30 of MI compared to the rest of patients.Conclusion. The association of HRPR to clopidogrel with the CYP2C19 (G681A) polymorphism was found during the entire observation period, with the P2RY12 (H1/H2) polymorphism on days 1-2 of MI, with the ITGB3 (T1565C) polymorphism on days 10-12 of MI. The association of HRPR to ASA with eNOS (T786C) polymorphism was found on days 1-2 of MI. Minor allele haplotypes of the CYP2C19 + ITGA2 + P2RY12 + eNOS genes and CYP2C19 + ITGA2 + eNOS genes were associated with a higher risk of developing HRPR to DAPT on days 28-30 of MI.

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Association of polymorphic variants of CYP2C19, P2RY12, ITGB3, ITGA2 and eNOS3 genes with high residual platelet reactivity while taking clopidogrel and acetylsalicylic acid at different terms of myocardial infarction

Pronko

Snezhitskiy

Stepuro

et al. 2023

Racionalʹnaâ farmakoterapiâ v kardiologii

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Frequency of CYP2C19, P2RY12, ITGB3, ITGA2, and eNOS3 gene polymorphism in patients with myocardial infarction

Pronko,

Snezhitskiy,

Stsiapura

et al. 2024

Vescì Nac. akad. navuk Belarusì, Ser. med. navuk

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The aim of the study was to assess the distribution of polymorphic variants G681A (*2) of the CYP2C19 gene, H1/H2 of the P2RY12 gene, T1565C of the ITGB3 gene, C807T of the ITGA2 gene, and T786C of the eNOS3 gene in the population of the Grodno region, and to study their associations with myocardial infarction (MI). The study of the population consists of 493 people, including 400 patients with MI aged 31 to 74 years and 93 people of the control group aged 32 to 60 years. Research data (clinical and genotyping performed by polymerase chain reaction) were analyzed using STATISTICA 10.0 software. The prevalence of carriage of genotypes associated with high residual platelet reactivity and variability in response to dual antiplatelet therapy among patients with MI was 25.2 % for the G681A polymorphic locus of the CYP2C19 gene (GA + AA), and for the H1/H2 polymorphic locus of the P2RY12 gene (H1/H2 + H2/H2) – 40.0 %, for the C807T polymorphic locus of the ITGA2 gene (CT + TT) – 65.8, for the T1565C polymorphic locus of the ITGB3 gene (TC + CC) – 25.5, for the polymorphic locus T786C of the eNOS gene (TC + CC) – 69.2 %. Among the individuals of the control group, the frequency of occurrence of these genotypes was 18.3, 46.2, 60.2, 37.6, 48.4 %, respectively. In patients with MI, compared to the control group, the TT genotype of the eNOS gene was less common (χ2 = 13.6, p = 0.0002), the CC genotype of the eNOS gene (χ2 = 5.4, p = 0.02) and the allele 786C of the eNOS gene (χ2 = 15.1, p = 0.0001) were more often detected. The carriage of the 786C allele of the eNOS gene increased the risk of MI in the studied population (OR = 2.0, 95 % CI: 1.41‒2.82, p = 0.0001). Gender differences were not found in the distribution of genotypes and alleles within the studied groups. There were no differences in carriage by the number of combinations of minor alleles between the control group and patients with MI. The most common combinations of minor alleles in both groups were comparable.

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Prospects for personalized rehabilitative medicine

Antonyuk

Yubitskaya

Гвозденко

et al. 2021

Bûlletenʹ fiziologii i patologii dyhaniâ

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A personalized approach, taking into account the genotype and individual characteristics of the patient, provides great opportunities for more effective prevention, treatment and rehabilitation. The review is focused on the main directions of personalized medicine. Prospects for the development of personalized rehabilitative medicine, including the use of non-drug methods, are described. Studies showing the influence of physical factors on the genome are discussed. It has been shown that the effects of physiotherapeutic factors are genetically determined. Advances in the field of physiogenetics indicate the need for developing and implementing personalized rehabilitative technologies.

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Pharmacogenetics of Antithrombotic Drugs: Status Update on the Problem

Cited by 3 publications

References 79 publications

Association of polymorphic variants of <i>CYP2C19</i>, <i>P2RY12</i>, <i>ITGB3</i>, <i>ITGA2</i> and <i>eNOS3</i> genes with high residual platelet reactivity while taking clopidogrel and acetylsalicylic acid at different terms of myocardial infarction

Association of polymorphic variants of <i>CYP2C19</i>, <i>P2RY12</i>, <i>ITGB3</i>, <i>ITGA2</i> and <i>eNOS3</i> genes with high residual platelet reactivity while taking clopidogrel and acetylsalicylic acid at different terms of myocardial infarction

Frequency of CYP2C19, P2RY12, ITGB3, ITGA2, and eNOS3 gene polymorphism in patients with myocardial infarction

Prospects for personalized rehabilitative medicine

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