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ABCC3 Polymorphisms and mRNA expression influence the concentration of a carboxylic acid metabolite in patients on clopidogrel and aspirin therapy
Luchessi, André Ducati; Concheiro, Marta; Germano, Juliana de Freitas; Silbiger, Vivian Nogueira; Bortolin, Raul Hernandes; Cruz, Angelines; Quintela, Oscar; Brion, Maria; Carracedo, Angel; Iñiguez, Andres; Bravo, Marisol; López-Rivadulla, Manuel; Hirata, Rosario Dominguez Crespo; Sousa, Amanda Guerra Moraes Rego; Hirata, Mario Hiroyuki.
Afiliação
  • Luchessi, André Ducati; School of Pharmaceutical Science, University of Sao Paulo. Sao Paulo. BR
  • Concheiro, Marta; Luis Concheiro Institute of Forensic Sciences, University of Santiago de Compostela. Santiago de Compostela. ES
  • Germano, Juliana de Freitas; School of Pharmaceutical Science, University of Sao Paulo. Sao Paulo. BR
  • Silbiger, Vivian Nogueira; Federal University of Rio Grande do Norte. Natal. BR
  • Bortolin, Raul Hernandes; Federal University of Rio Grande do Norte. Natal. BR
  • Cruz, Angelines; Luis Concheiro Institute of Forensic Sciences, University of Santiago de Compostela. Santiago de Compostela. ES
  • Quintela, Oscar; Department of Madrid, National Institute of Toxicology and Forensic Science. Madrid. ES
  • Brion, Maria; Genetics of Cardiovascular and Ophthalmological Diseases, Health Research Institute of Santiago de Compostela (IDIS). Genomic Medicine, University of Santiago de Compostela, IDIS, CIBERER. Santiago de Compostela. ES
  • Carracedo, Angel; Genomic Medicine, University of Santiago de Compostela, IDIS, CIBERER. Santiago de Compostela. ES
  • Iñiguez, Andres; Cardiology Service, Alvaro Cunqueiro Hospital. Vigo. ES
  • Bravo, Marisol; Cardiology Service, Alvaro Cunqueiro Hospital. Vigo. ES
  • López-Rivadulla, Manuel; Luis Concheiro Institute of Forensic Sciences, University of Santiago de Compostela. Santiago de Compostela. ES
  • Hirata, Rosario Dominguez Crespo; School of Pharmaceutical Science, University of Sao Paulo. Sao Paulo. BR
  • Sousa, Amanda Guerra Moraes Rego; Dante Pazzanese Institute of Cardiology. Sao Paulo. BR
  • Hirata, Mario Hiroyuki; School of Pharmaceutical Science, University of Sao Paulo. Sao Paulo. BR
Basic clin. pharmacol. toxicol ; 120(5): 466-474, 2017.
Article em En | SES-SP, SESSP-IDPCPROD, SES-SP | ID: biblio-1060446
Biblioteca responsável: BR79.1
Localização: BR79.1
ABSTRACT
Acetylsalicylic acid (ASA) and clopidogrel combined therapy has been reported to be beneficial in patients with acute coronary syndrome (ACS). Antiplatelet drug resistance, especially to clopidogrel, is a multifactorial phenomenon that affects a large number of ACS patients. The genetic contribution to this drug response is not fully elucidated. We investigated the relationship of ABC-type efflux subfamily C member 3 (ABCC3) polymorphisms and mRNA expression with plasma concentrations of clopidogrel, salicylic acid (SA) and a carboxylic acid metabolite (CAM). Clopidogrel, CAM and SA plasma concentrations were measured simultaneously by liquid chromatography-tandem mass spectrometry (LCMS/MS) from 83 ACS patients undergoing percutaneous coronary intervention. ABCC3 (rs757421, rs733392 and rs739923) and CYP2C19*2 (rs4244285) polymorphisms as well as mRNA expression were evaluated. A positive correlation was found between CAM concentrations and ABCC3 mRNA expression (r = 0.494, p < 0.0001). Patients carrying genotype AA (rs757421 variant) had higher CAM concentrations and ABCC3 mRNA expression as compared to those of GG + GA carriers (p = 0.017). A multiple linear regression analysis revealed that ABCC3 mRNA expression (p = 0.017), rs757421 AA genotype (p = 0.001), blood collection time (p = 0.018) and clopidogrel dose (p = 0.001) contributed to the concentration of CAM. No associations were observed for the CYP2C19*2 polymorphism...
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Texto completo: 1 Coleções: 06-national / BR Base de dados: SES-SP / SESSP-IDPCPROD Assunto principal: Pacientes / Polimorfismo Genético / RNA Mensageiro Idioma: En Revista: Basic clin. pharmacol. toxicol Ano de publicação: 2017 Tipo de documento: Article
Texto completo
Adicionar na Minha BVS
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XML
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Texto completo: 1 Coleções: 06-national / BR Base de dados: SES-SP / SESSP-IDPCPROD Assunto principal: Pacientes / Polimorfismo Genético / RNA Mensageiro Idioma: En Revista: Basic clin. pharmacol. toxicol Ano de publicação: 2017 Tipo de documento: Article