title: Chronic kidney disease status modifies the association of CYP2C19 polymorphism in predicting clinical outcomes following coronary stent implantation.
abstract: BACKGROUND
  There is some controversy regarding the effect of CYP2C19 polymorphism on clinical outcome in patients with dual antiplatelet therapy. Chronic kidney disease (CKD) is associated with increased risk of cardiovascular event, but the association between the possession of CYP2C19 loss-of-function (LOF) alleles and clinical outcome according to the presence of CKD is poorly understood. The aim of this study was to investigate whether CKD status modifies the association of CYP2C19 polymorphism in predicting outcomes in a prospective cohort study.
  
  
  METHODS
  We enrolled 331 patients following coronary stent implantation. Patients were divided into two groups: CKD (n=154) and non-CKD (n=177). Platelet reactivity and CYP2C19 polymorphism were examined. The subjects were further divided into two groups according to the possession of CYP2C19 LOF alleles: carriers and non-carriers. Patients were followed up and clinical events were evaluated according to CKD and carrier status.
  
  
  RESULTS
  The proportion of high platelet reactivity was significantly higher in carriers than in non-carriers in both CKD (42.4% versus 21.7%; P=0.016) and non-CKD groups (34.3% versus 3.7%; P<0.001). In the non-CKD group alone, the incidence of cardiovascular events was significantly higher in carriers than in non-carriers (13.7% versus 1.7%; P=0.013). Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in carriers than in non-carriers in the non-CKD group (log-rank test: P=0.013) and there was no significant difference in the CKD group (log-rank test: P=0.591). Multivariate analysis identified carriers as an independent predictor of cardiovascular events only in the non-CKD group alone (hazard ratio: 8.048; 95% confidence interval: 1.066 to 60.757; P=0.043).
  
  
  CONCLUSIONS
  CYP2C19 polymorphism significantly correlates with clinical outcome in non-CKD patients, and CKD status modifies the association of CYP2C19 polymorphism in predicting clinical outcomes following coronary stent implantation.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tabata
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Japan. Electronic address: shokimot@kumamoto-u.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Hokimoto
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Akasaka
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Arima
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kaikita
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kumagae
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Morita
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Miyazaki
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Oniki
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Matsui
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000150:complications* / Q000235:genetics / Q000601:surgery / Q000628:therapy*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000235:genetics; D015607:Stents; D016896:Treatment Outcome
chemical_list: D065731:Cytochrome P-450 CYP2C19
keywords: coronary disease; genetics; kidney; pharmacology; stents