Increased clopidogrel response is associated with ABCC3 expression: a pilot study.
Clin Chim Acta
; 413(3-4): 417-21, 2012 Feb 18.
Article
em En
| MEDLINE
| ID: mdl-22040781
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, <2.5×10(-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 2.5×10(-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ticlopidina
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Regulação da Expressão Gênica
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Proteínas Associadas à Resistência a Múltiplos Medicamentos
Tipo de estudo:
Risk_factors_studies
Limite:
Aged
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Chim Acta
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Holanda