The ABCB1, CYP2C19, CYP3A5 and CYP4F2 genetic polymorphisms and platelet reactivity in the early phases of acute coronary syndromes

Mirzaev K. B., Rytkin E., Ryzhikova K. A., Grishina E. A., Sozaeva Z. A., Fedorinov D. S., Konova O. D., Gilyarov M. Yu., Belyakova G. A., Andreev D. A., Sy'chev D. A.

Drug Metabolism and Personalized Therapy

Vol.33, Issue3, P. 109-118

Опубликовано: 2018

Тип ресурса: Статья

DOI:10.1515/dmpt-2018-0006

Аннотация:

The aim was to study seven polymorphic markers of genes encoding proteins involved in the absorption, metabolism and pharmacokinetics of clopidogrel among patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Eighty-one ACS and PCI patients older than 18 years and treated with dual antiplatelet therapy were enrolled in the study. Platelet function testing and ABCB1, CYP2C19, CYP3A5 and CYP4F2 genotyping were performed. The predictive role of categorical variables, such as genotypes (carriers and non-carriers of polymorphism), on platelet reactivity (platelet reactivity units [PRU] platelet inhibition [PI]) was assessed by logistic regression (for categorical outcomes) and linear regression (for continuous outcomes) analysis. A p-value<0.05 was considered significant. The allele frequencies were estimated by gene counting, and Hardy-Weinberg equilibrium was tested using the chi-square test. Regarding clopidogrel response, 62 patient

Ключевые слова:

acute coronary syndrome; clopidogrel; cytochrome P450; percutaneous coronary intervention; pharmacogenetics; polymorphism

acetylsalicylic acid; beta adrenergic receptor blocking agent; calcium channel blocking agent; clopidogrel; cytochrome P450; cytochrome P450 2C19; cytochrome P450 3A5; cytochrome P450 4F2; dipeptidyl carboxypeptidase inhibitor; diuretic agent; genomic DNA; hydroxymethylglutaryl coenzyme A reductase inhibitor; multidrug resistance protein 1; proton pump inhibitor; unclassified drug; ABCB1 protein, human; antithrombocytic agent; clopidogrel; CYP2C19 protein, human; CYP3A5 protein, human; CYP4F2 protein, human; cytochrome P450 2C19; cytochrome P450 3A; cytochrome P450 family 4; ABCB1 gene; acute coronary syndrome; adult; aged; Article; blood sampling; Caucasian; CYP2C19 gene; CYP3A5 gene; CYP4F2 gene; DNA extraction; drug response; dual antiplatelet therapy; female; gene frequency; gene linkage disequilibrium; genetic polymorphism; genotype; human; loading drug dose; major clinical study; male; percutaneous coronary intervention; platelet reactivity; acute coronary syndrome; blood; chemis

Язык текста: Английский

ISSN: 2363-8915

Mirzaev K. B. Karin Badavievich 1991-

Rytkin E.

Ryzhikova K. A.

Grishina E. A.

Sozaeva Z. A.

Fedorinov D. S. Denis Sergeevich 1996-

Konova O. D.

Gilyarov M. Yu. Mikhail Yuryevich 1967-

Belyakova G. A. Galina Aleksandrovna 1951-

Andreev D. A. Denis Anatolyevich 1968-

Sy'chev D. A. Dmitrij Alekseevich 1975-

Мирзаев К. Б. Карин Бадавиевич 1991-

Рyткин Е.

Рyжикова К. А.

Гришина Е. А.

Созаева З. А.

Федоринов Д. С. Денис Сергеевич 1996-

Конова О. Д.

Гиляров М. Ю. Михаил Юрьевич 1967-

Белякова Г. А. Галина Александровна 1951-

Андреев Д. А. Денис Анатольевич 1968-

Сычев Д. А. Дмитрий Алексеевич 1975-

The ABCB1, CYP2C19, CYP3A5 and CYP4F2 genetic polymorphisms and platelet reactivity in the early phases of acute coronary syndromes

Текст визуальный непосредственный

Drug Metabolism and Personalized Therapy

Walter de Gruyter GmbH

Vol.33, Issue3 P. 109-118

2018

Статья

acute coronary syndrome clopidogrel cytochrome P450 percutaneous coronary intervention pharmacogenetics polymorphism

acetylsalicylic acid beta adrenergic receptor blocking agent calcium channel blocking agent clopidogrel cytochrome P450 cytochrome P450 2C19 cytochrome P450 3A5 cytochrome P450 4F2 dipeptidyl carboxypeptidase inhibitor diuretic agent genomic DNA hydroxymethylglutaryl coenzyme A reductase inhibitor multidrug resistance protein 1 proton pump inhibitor unclassified drug ABCB1 protein, human antithrombocytic agent clopidogrel CYP2C19 protein, human CYP3A5 protein, human CYP4F2 protein, human cytochrome P450 2C19 cytochrome P450 3A cytochrome P450 family 4 ABCB1 gene acute coronary syndrome adult aged Article blood sampling Caucasian CYP2C19 gene CYP3A5 gene CYP4F2 gene DNA extraction drug response dual antiplatelet therapy female gene frequency gene linkage disequilibrium genetic polymorphism genotype human loading drug dose major clinical study male percutaneous coronary intervention platelet reactivity acute coronary syndrome blood chemis

The aim was to study seven polymorphic markers of genes encoding proteins involved in the absorption, metabolism and pharmacokinetics of clopidogrel among patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Eighty-one ACS and PCI patients older than 18 years and treated with dual antiplatelet therapy were enrolled in the study. Platelet function testing and ABCB1, CYP2C19, CYP3A5 and CYP4F2 genotyping were performed. The predictive role of categorical variables, such as genotypes (carriers and non-carriers of polymorphism), on platelet reactivity (platelet reactivity units [PRU] platelet inhibition [PI]) was assessed by logistic regression (for categorical outcomes) and linear regression (for continuous outcomes) analysis. A p-value<0.05 was considered significant. The allele frequencies were estimated by gene counting, and Hardy-Weinberg equilibrium was tested using the chi-square test. Regarding clopidogrel response, 62 patient