title: Rapid and portable, lab-on-chip, point-of-care genotyping for evaluating clopidogrel metabolism.
abstract: BACKGROUND
  Dual antiplatelet therapy with aspirin and a platelet P2Y12 receptor inhibitors (clopidogrel, prasugrel, ticagrelor) is a cornerstone of antithrombotic treatment in patients with acute coronary syndromes (ACS). Clopidogrel has been the standard of care for nearly a decade; however, its clinical efficacy is influenced by a considerable inter-patient variability in response, clearly associated to cytochrome P (CYP) enzyme genetic variations. We used a novel point-of-care lab-on-chip instrument to genotype ACS patients in order to identify carriers of the ATB-binding cassette ABCB1 3435, CYP2C19*2 and CYPC2C19*17 alleles and adjust the pharmacological approach accordingly.
  
  
  RESULTS
  Between October 2012 and January 2013, 160 ACS patients were enrolled at the Cardiology Unit of the Ospedale Niguarda Cà Granda and genotyped at the patients' point-of-care using the newly developed Q3 portable real-time PCR instrument, which remarkably scored the CYP2C19*2, CYP2C19*17, and ABCB1 3435 alleles in a time of 70 min from DNA extraction to final genotype calls; concordance with the other gold-standard genotyping techniques was 100%.
  
  
  CONCLUSIONS
  The Q3 instrument proved to be as reliable as the current conventional techniques. As genotyping in the ACS setting cannot be delegated to centralised clinical laboratories for reasons of time, genotyping at the patients' bedside provides an opportunity to conduct large-scale randomised trials in order to assess whether adding genotype data to clinical variables improves clinical outcomes.
authors.affiliation: Division of Cardiology, Azienda Sanitaria Locale 3, San Francesco Hospital, Nuoro, Italy; IV Division of Cardiology, Azienda Ospedaliera Ospedale Cà Granda, Milan, Italy. Electronic address: marziliano@aslnuoro.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Marziliano
authors.affiliation: Division of Cardiology, Azienda Ospedaliero Universitaria di Parma, Parma, Italy.
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Notarangelo
authors.affiliation: STMicroelectronics, Monza, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cereda
authors.affiliation: Department of Biochemistry, University of Milan, Milan, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Caporale
authors.affiliation: Division of Cardiology, Azienda Ospedaliero Universitaria di Parma, Parma, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Coppini
authors.affiliation: Division of Cardiology, Azienda Ospedaliero Universitaria di Parma, Parma, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Demola
authors.affiliation: Division of Cardiology, Azienda Ospedaliero Universitaria di Parma, Parma, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Guidorossi
authors.affiliation: Division of Cardiology, Azienda Ospedaliero Universitaria di Parma, Parma, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Crocamo
authors.affiliation: Division of Cardiology, Azienda Ospedaliero Universitaria di Parma, Parma, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Pigazzani
authors.affiliation: Division of Cardiology, Azienda Ospedaliero Universitaria di Parma, Parma, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Boffetti
authors.affiliation: Division of Cardiology, Azienda Ospedaliero Universitaria di Parma, Parma, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: del Giudice
authors.affiliation: Department of Biochemistry, University of Milan, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Orsini
authors.affiliation: Department of Biochemistry, University of Milan, Milan, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Pirola
authors.affiliation: Department of Biochemistry, University of Milan, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cocci
authors.affiliation: University of Parma, Parma, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Manzalini
authors.affiliation: Division of Cardiology, Azienda Sanitaria Locale 3, San Francesco Hospital, Nuoro, Italy.
authors.forename: Gavino
authors.initials: G
authors.lastname: Casu
authors.affiliation: Department of Biochemistry, University of Milan, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bianchessi
authors.affiliation: Division of Cardiology, Azienda Ospedaliero Universitaria di Parma, Parma, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Ardissino
authors.affiliation: IV Division of Cardiology, Azienda Ospedaliera Ospedale Cà Granda, Milan, Italy.
authors.forename: Piera Angelica
authors.initials: PA
authors.lastname: Merlini
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D054058:Acute Coronary Syndrome / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D000483:Alleles; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D056656:Lab-On-A-Chip Devices; D019095:Point-of-Care Systems; D011110:Polymorphism, Genetic / Q000235:genetics; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
keywords: ABCB1; CYP2C19*2; Clopidogrel