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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 [Anatol J Cardiol]
Anatol J Cardiol. 2017; 17(4): 303-312 | DOI: 10.14744/AnatolJCardiol.2016.7390  

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

Maria Henar Garcia - Lagunar1, Luciano Consuegra - Sanchez2, Pablo Conesa- Zamora3, Javier Ruiz - Cosano4, Federico Soria Arcos2, Luis Garci&769;a De Guadiana3, Pedro Cano Vivar2, Juan Antonio Castillo - Moreno2, Antonio Melgarejo - Moreno2
1Departments of Hospital Pharmacy, Santa Lucía General University Hospital (HGUSL); Cartagena-Spain
2Cardiology, Santa Lucía General University Hospital (HGUSL); Cartagena-Spain
3Clinical Analysis, Santa Lucía General University Hospital (HGUSL); Cartagena-Spain
4Pathology, Santa Lucía General University Hospital (HGUSL); Cartagena-Spain

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 geno- types (CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*17, CYP3A4*1B, and PON1-Q192R) were evaluated with TaqMan® and KASPar® assays. Plate- let 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: 000-00)

Keywords: acute coronary syndrome; clopidogrel; platelet; aggregometry; polymorphism


Maria Henar Garcia - Lagunar, Luciano Consuegra - Sanchez, Pablo Conesa- Zamora, Javier Ruiz - Cosano, Federico Soria Arcos, Luis Garci&769;a De Guadiana, Pedro Cano Vivar, Juan Antonio Castillo - Moreno, Antonio Melgarejo - Moreno. Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome. Anatol J Cardiol. 2017; 17(4): 303-312

Corresponding Author: Maria Henar Garcia - Lagunar, Spain


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