title: Feasibility of a microarray-based point-of-care CYP2C19 genotyping test for predicting clopidogrel on-treatment platelet reactivity.
abstract: Clopidogrel is a prodrug which is converted into active metabolite by cytochrome P450 isoenzyme, CYP2C19. Numerous polymorphisms of CYP2C19 are reported, and a strong link exists between loss-of-function (LOF) or gain-of-function polymorphisms, clopidogrel metabolism, and clinical outcome. Hence, a fully automated point-of-care CYP2C19 genotyping assay is more likely to bring personalized antiplatelet therapy into real practice. We assessed the feasibility of the Verigene 2C19/CBS Nucleic Acid Test, a fully automated microarray-based assay, compared to bidirectional sequencing, and performed VerifyNow P2Y12 assay to evaluate the effect of CYP2C19 polymorphisms on on-treatment platelet reactivity in 57 Korean patients treated with clopidogrel after percutaneous coronary intervention. The Verigene 2C19/CBS assay identified ∗2, ∗3, and ∗17 polymorphisms with 100% concordance to bidirectional sequencing in 180 minutes with little hands-on time. Patients were classified into 4 groups: extensive (∗1/∗1; n = 12, 21.1%), intermediate (∗1/∗2, ∗1/∗3; n = 33, 57.9%), poor (∗2/∗2, ∗2/∗3, and ∗3/∗3; n = 11, 19.3%), and ultrarapid metabolizers (∗1/∗17; n = 1, 1.8%). The prevalence of the CYP2C19  ∗2, ∗3, and ∗17 alleles was 36.0%, 12.3%, and 0.9%. Platelet reactivity showed gene dose response according to the number of CYP2C19 LOF allele. In conclusion, the Verigene 2C19/CBS assay gave accurate CYP2C19 genotype results which were in well match with the differing on-treatment platelet reactivity.
authors.affiliation: Department of Laboratory Medicine, Bucheon St. Mary's Hospital, 2 Sosa-dong, Wonmi-gu, Gyeonggi-do, Bucheon-si 420-717, Republic of Korea.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Chae
authors.forename: Myungshin
authors.initials: M
authors.lastname: Kim
authors.forename: Yoon-Seok
authors.initials: YS
authors.lastname: Koh
authors.forename: Byung-Hee
authors.initials: BH
authors.lastname: Hwang
authors.forename: Min-Kyu
authors.initials: MK
authors.lastname: Kang
authors.forename: Yonggoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Hae-Il
authors.initials: HI
authors.lastname: Park
authors.forename: Kiyuk
authors.initials: K
authors.lastname: Chang
mesh_terms: D000368:Aged; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D010976:Platelet Count; D019095:Point-of-Care Systems; D011110:Polymorphism, Genetic; D057285:Precision Medicine; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine