title: Pharmacogenomics of anti-platelet therapy focused on peripheral blood cells of coronary arterial disease patients.
abstract: BACKGROUND
  To investigate genes differentially expressed in peripheral blood cells (PBCs) from patients with coronary arterial disease (CAD) under double anti-platelet therapy.
  
  
  METHODS
  Twenty-six CAD patients that were submitted to percutaneous coronary intervention (PCI) were selected to participate in this study. These patients took 100mg/day of acetylsalicylic acid (ASA) and 75mg/day of clopidogrel. Blood samples were collected before PCI to evaluate platelet reactivity using VerifyNow ASA and P2Y12 assays (Accumetrics). The patients were stratified into 4 quartiles based on ASA reaction units (ARUs) and P2Y12 reaction units (PRUs). Quartile 1 (Q1) patients were classified as responders and quartile 4 (Q4) patients as non-responders. Global mRNA expression from Q1 to Q4 was analyzed by microarray using the GeneChip Exon 1.0 ST array (Affymetrix) and was confirmed by RT-qPCR.
  
  
  RESULTS
  Patients with ARU or PRU values within the first quartile (Q1, ARU<390 and PRU<151) were considered responders, while those who had ARU or PRU within the fourth quartile (Q4, ARU>467 and PRU>260) were considered nonresponders. The risk factors associated for CAD showed expected frequencies and no difference was found between Q1 and Q4. Microarray analysis identified 117 genes differentially expressed for ASA and 29 for clopidogrel between Q1 and Q4 groups (p<0.01, FC>1.2).
  
  
  CONCLUSIONS
  The variation in response to ASA may be related with an increased expression of IGF1 and IGF1R, as well as a response to clopidogrel can be affected by pharmacokinetic change related to the reverse transport pathway by increased expression of ABCC3.
authors.affiliation: School of Pharmaceutical Sciences, University of Sao Paulo, Brazil. Electronic address: adluchessi@usp.br.
authors.forename: André Ducati
authors.initials: AD
authors.lastname: Luchessi
authors.forename: Vivian Noguiea
authors.initials: VN
authors.lastname: Silbiger
authors.forename: Rosario Dominguez Crespo
authors.initials: RD
authors.lastname: Hirata
authors.forename: Lidio Gonçalves
authors.initials: LG
authors.lastname: Lima-Neto
authors.forename: Débora
authors.initials: D
authors.lastname: Cavichioli
authors.forename: Andres
authors.initials: A
authors.lastname: Iñiguez
authors.forename: Marisol
authors.initials: M
authors.lastname: Bravo
authors.forename: Guillermo
authors.initials: G
authors.lastname: Bastos
authors.forename: Amanda Guerra Morais Rego
authors.initials: AG
authors.lastname: Sousa
authors.forename: Maria
authors.initials: M
authors.lastname: Brión
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.forename: Mario Hiroyuki
authors.initials: MH
authors.lastname: Hirata
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004334:Drug Administration Schedule; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D001241:Aspirin; D000077144:Clopidogrel; D007334:Insulin-Like Growth Factor I; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010975:Platelet Aggregation Inhibitors; D017526:Receptor, IGF Type 1; D013988:Ticlopidine; C583557:IGF1 protein, human; C114462:multidrug resistance-associated protein 3
keywords: Acetylsalicylic acid; Clopidogrel; Microarray; Pharmacogenomics