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Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome

OBJECTIVE: To evaluate the contribution of six polymorphisms to the platelet reactivity in patients with acute coronary syndrome (ACS) treated with clopidogrel. METHODS: Cross-sectional study of 278 consecutive patients with ACS. Detailed clinical information for each patient was collected and genot...

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Autores principales: García-Lagunar, María Henar, Consuegra-Sánchez, Luciano, Conesa-Zamora, Pablo, Ruiz-Cosano, Javier, Arcos, Federico Soria, de Guadiana, Luis García, Vivar, Pedro Cano, Castillo-Moreno, Juan Antonio, Melgarejo-Moreno, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Kare Publishing 2017
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469111/
https://www.ncbi.nlm.nih.gov/pubmed/28179614
http://dx.doi.org/10.14744/AnatolJCardiol.2016.7390
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author García-Lagunar, María Henar
Consuegra-Sánchez, Luciano
Conesa-Zamora, Pablo
Ruiz-Cosano, Javier
Arcos, Federico Soria
de Guadiana, Luis García
Vivar, Pedro Cano
Castillo-Moreno, Juan Antonio
Melgarejo-Moreno, Antonio
author_facet García-Lagunar, María Henar
Consuegra-Sánchez, Luciano
Conesa-Zamora, Pablo
Ruiz-Cosano, Javier
Arcos, Federico Soria
de Guadiana, Luis García
Vivar, Pedro Cano
Castillo-Moreno, Juan Antonio
Melgarejo-Moreno, Antonio
author_sort García-Lagunar, María Henar
collection PubMed
description OBJECTIVE: To evaluate the contribution of six polymorphisms to the platelet reactivity in patients with acute coronary syndrome (ACS) treated with clopidogrel. METHODS: Cross-sectional study of 278 consecutive patients with ACS. Detailed clinical information for each patient was collected and genotypes (CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*17, CYP3A4*1B, and PON1-Q192R) were evaluated with TaqMan(®) and KASPar(®) assays. Platelet reactivity was measured with VerifyNow(®). RESULTS: Mean age of patients was 66±11 years and 182 (65.5%) patients presented ACS without ST-segment elevation. A total of 206 (74.1%) patients presented poor response to clopidogrel (PRC). CYP2C19*2 polymorphism (p=0.038) was associated with PRC in the univariate setting. In the multiple logistic regression analysis, the risk factors for PRC were the presence of CYP3A4*1B allele (odds ratio [OR] 4.03; 95% confidence interval [CI] 1.01–16.34), age (OR 1.43; 95% CI 1.03–2.00), and body mass index (OR 4.05; 95% CI 1.21–13.43), whereas elevated hemoglobin was a protective factor. Discrimination of PRC through the model that included the six polymorphisms added modest information to the model based on clinical variables (C statistic difference 3.9%). CONCLUSION: CYP3A4*1B allele may be an independent determinant of PRC in patients with ACS, although the variability in response to clopidogrel explained by the six polymorphisms is poor when compared to clinical variables. (Anatol J Cardiol 2017; 17: 303-12)
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spelling pubmed-54691112017-06-28 Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome García-Lagunar, María Henar Consuegra-Sánchez, Luciano Conesa-Zamora, Pablo Ruiz-Cosano, Javier Arcos, Federico Soria de Guadiana, Luis García Vivar, Pedro Cano Castillo-Moreno, Juan Antonio Melgarejo-Moreno, Antonio Anatol J Cardiol Original Investigation OBJECTIVE: To evaluate the contribution of six polymorphisms to the platelet reactivity in patients with acute coronary syndrome (ACS) treated with clopidogrel. METHODS: Cross-sectional study of 278 consecutive patients with ACS. Detailed clinical information for each patient was collected and genotypes (CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*17, CYP3A4*1B, and PON1-Q192R) were evaluated with TaqMan(®) and KASPar(®) assays. Platelet reactivity was measured with VerifyNow(®). RESULTS: Mean age of patients was 66±11 years and 182 (65.5%) patients presented ACS without ST-segment elevation. A total of 206 (74.1%) patients presented poor response to clopidogrel (PRC). CYP2C19*2 polymorphism (p=0.038) was associated with PRC in the univariate setting. In the multiple logistic regression analysis, the risk factors for PRC were the presence of CYP3A4*1B allele (odds ratio [OR] 4.03; 95% confidence interval [CI] 1.01–16.34), age (OR 1.43; 95% CI 1.03–2.00), and body mass index (OR 4.05; 95% CI 1.21–13.43), whereas elevated hemoglobin was a protective factor. Discrimination of PRC through the model that included the six polymorphisms added modest information to the model based on clinical variables (C statistic difference 3.9%). CONCLUSION: CYP3A4*1B allele may be an independent determinant of PRC in patients with ACS, although the variability in response to clopidogrel explained by the six polymorphisms is poor when compared to clinical variables. (Anatol J Cardiol 2017; 17: 303-12) Kare Publishing 2017-04 2017-02-01 /pmc/articles/PMC5469111/ /pubmed/28179614 http://dx.doi.org/10.14744/AnatolJCardiol.2016.7390 Text en Copyright: © 2017 Turkish Society of Cardiology http://creativecommons.org/licenses/by-nc-sa/4.0 This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
spellingShingle Original Investigation
García-Lagunar, María Henar
Consuegra-Sánchez, Luciano
Conesa-Zamora, Pablo
Ruiz-Cosano, Javier
Arcos, Federico Soria
de Guadiana, Luis García
Vivar, Pedro Cano
Castillo-Moreno, Juan Antonio
Melgarejo-Moreno, Antonio
Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome
title Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome
title_full Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome
title_fullStr Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome
title_full_unstemmed Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome
title_short Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome
title_sort genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469111/
https://www.ncbi.nlm.nih.gov/pubmed/28179614
http://dx.doi.org/10.14744/AnatolJCardiol.2016.7390
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