Increased clopidogrel response is associated with ABCC3 expression: A pilot study

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Luchessi, Andre Ducati ^[1] ; Silbiger, Vivian Nogueira ^[2] ; Cerda, Alvaro ; Crespo Hirata, Rosario Dominguez ; Carracedo, Angel ^[3] ; Brion, Maria ^{[3, 4]} ; Iniguez, Andres ^[5] ; Bravo, Marisol ^[5] ; Bastos, Guillermo ^[5] ; Morais Rego Sousa, Amanda Guerra ^[6] ; Hirata, Mario Hiroyuki

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, BR-05508900 Sao Paulo - Brazil

^[2] Univ Fed Rio Grande do Norte, Fac Pharm, BR-59072970 Natal, RN - Brazil

^[3] Univ Santiago de Compostela, CIBERER, Fdn Med Xen, Grp Med Xen, Santiago De Compostela - Spain

^[4] CHUS, Santiago De Compostela - Spain

^[5] Hosp Meixoeiro, Vigo - Spain

^[6] Inst Dante Pazzanese Estado Sao Paulo, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinica Chimica Acta; v. 413, n. 3-4, p. 417-421, FEB 18 2012.
• Citações Web of Science: 11

Resumo

Background: The aim of this study was investigate the relationship between ABCB1 and ABCC3 gene expressions in peripheral blood cells (PBC) and the response to clopidogrel in patients with coronary arterial disease (CAD). Methods: Twenty-six male CAD patients (50-70 years) under treatment with clopidogrel (75 mg/day) for at least 5 days were selected. Blood samples were obtained to evaluate platelet reactivity and ABCB1 and ABCC3 mRNA expression. Platelet reactivity was measured in P2Y12 Reaction Units (PRU) using VerifyNow. RNA was extracted from PBC and mRNA levels were measured by qPCR, using GAPD as a reference gene. Results: Platelet response to clopidogrel was categorized in to PRU quartiles. Individuals with PRU values within the first quartile (Q1, <151 units) were considered good responders, while those who had PRU within the fourth quartile (Q4. PRU>260) were considered non-responders. ABCC3 was 1.7 times more expressed in Q4 than in Q1 PRU group (p=0.048). Moreover, CAD patients with low ABCC3 expression (Qe1, <2.5x10(-3)) had higher probability to have a good response to clopidogrel (OR: 18.00, 95%CI: 1.90-169.99, p=0.001). Univariate linear regression analysis demonstrated that low ABCC3 mRNA expression contributed with a reduction of 73 PRU in relation to the patients with expression value higher than 2.5x10(-3) (p=0.027). Neither ABCB1 mRNA levels nor clinical variables studied influenced PRU values. Conclusions: Low ABCC3 mRNA expression in peripheral blood cells is associated with increased clopidogrel response, but further studies are needed to describe the functional relationship of clopidogrel with the ABCC3. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 06/03487-4 - Transcriptoma e proteoma em sangue periférico para pesquisa de novos marcadores de doenças cardiovasculares: estudo em infarto agudo do miocárdio
• Beneficiário: Mario Hiroyuki Hirata
• Modalidade de apoio: Auxílio à Pesquisa - Regular