title: Predicting clopidogrel response using DNA samples linked to an electronic health record.
abstract: Variants in ABCB1 and CYP2C19 have been identified as predictors of cardiac events during clopidogrel therapy initiated after myocardial infarction (MI) or percutaneous coronary intervention (PCI). In addition, PON1 has recently been associated with stent thrombosis. The reported effects of these variants have not yet been replicated in a real-world setting. We used BioVU, the Vanderbilt DNA repository linked to de-identified electronic health records (EHRs), to find data on patients who were on clopidogrel treatment after an MI and/or a PCI; among these, we identified those who had experienced one or more recurrent cardiac events while on treatment (cases, n = 225) and those who had not experienced any cardiac event while on treatment (controls, n = 468). We found that CYP2C19*2 (hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.16-2.06, P = 0.003) and ABCB1 (HR 1.28, 95% CI 1.04-1.57, P = 0.018), but not PON1 (HR 0.91, 95% CI 0.73-1.12, P = 0.370), were associated with recurrent events. In this population, genetic signals for clopidogrel resistance in ABCB1 and CYP2C19 were replicated, supporting the use of EHRs for pharmacogenomic studies. Our data do not show an association between PON1 and recurrent cardiovascular events.
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Delaney
authors.forename: A H
authors.initials: AH
authors.lastname: Ramirez
authors.forename: E
authors.initials: E
authors.lastname: Bowton
authors.forename: J M
authors.initials: JM
authors.lastname: Pulley
authors.forename: M A
authors.initials: MA
authors.lastname: Basford
authors.forename: J S
authors.initials: JS
authors.lastname: Schildcrout
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.forename: R
authors.initials: R
authors.lastname: Zink
authors.forename: M
authors.initials: M
authors.lastname: Oetjens
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.forename: J H
authors.initials: JH
authors.lastname: Cleator
authors.forename: E
authors.initials: E
authors.lastname: Jahangir
authors.forename: M D
authors.initials: MD
authors.lastname: Ritchie
authors.forename: D R
authors.initials: DR
authors.lastname: Masys
authors.forename: D M
authors.initials: DM
authors.lastname: Roden
authors.forename: D C
authors.initials: DC
authors.lastname: Crawford
authors.forename: J C
authors.initials: JC
authors.lastname: Denny
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000235:genetics; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D030561:Databases, Nucleic Acid; D057286:Electronic Health Records; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D010597:Pharmacogenetics / Q000379:methods*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D015607:Stents; D013927:Thrombosis / Q000188:drug therapy*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D013988:Ticlopidine