title: Increased clopidogrel response is associated with ABCC3 expression: a pilot study.
abstract: 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.
authors: Faculty of Pharmaceutical Science, Department of Clinical and Toxicological Analyses, University of Sao Paulo, Sao Paulo, Brazil. adluchessi@usp.br
authors: André Ducati
authors: AD
authors: Luchessi
authors: Vivian Nogueira
authors: VN
authors: Silbiger
authors: Alvaro
authors: A
authors: Cerda
authors: Rosario Dominguez Crespo
authors: RD
authors: Hirata
authors: Angel
authors: A
authors: Carracedo
authors: Maria
authors: M
authors: Brion
authors: Andres
authors: A
authors: Iñiguez
authors: Marisol
authors: M
authors: Bravo
authors: Guillermo
authors: G
authors: Bastos
authors: Amanda Guerra Morais Rego
authors: AG
authors: Sousa
authors: Mario Hiroyuki
authors: MH
authors: Hirata
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000368:Aged; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010865:Pilot Projects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000077144:Clopidogrel; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D013988:Ticlopidine; C513055:ABCB1 protein, human; C114462:multidrug resistance-associated protein 3