title: Prevalence and significance of CYP2C19*2 and CYP2C19*17 alleles in a New Zealand acute coronary syndrome population.
abstract: BACKGROUND
  High on-treatment platelet reactivity has been associated with poor outcomes following acute coronary syndromes (ACS). Both the loss of function CYP2C19*2 allele and the gain of function CYP2C19*17 allele along with a range of clinical characteristics have been associated with variation in the response to clopidogrel.
  
  
  OBJECTIVE
  The study aims to examine the frequency of CYP2C19 variants and understand the factors associated with on-treatment platelet reactivity in a New Zealand ACS population.
  
  
  METHODS
  We prospectively enrolled 312 ACS patients. We collected clinical characteristics and measured on-treatment platelet reactivity using two validated point-of-care assays, VerifyNow and Multiplate. DNA was extracted and CYP2C19*2 and *17 alleles were identified using real-time polymerase chain reaction.
  
  
  RESULTS
  CYP2C19*2 or CYP2C19*17 alleles were observed in 101 (32%) and 106 (34%) of patients, respectively, with significant differences in distribution by ethnicity. In Maori and Pacific Island patients, 47% (confidence interval (CI) 31-63%) had CYP2C19*2 and 11% (CI 4-19%) CYP2C19*17 compared with 26% (CI 19-32%) and 41% (CI 32-49%) in white people. Carriage of CYP2C19*2 alleles was associated with higher levels of platelet reactivity measured by either assay, but we observed no relationship between platelet reactivity and CYP2C19*17. In multivariate analysis diabetes, clopidogrel dose and CYP2C19*2 status were all significant independent predictors of platelet reactivity.
  
  
  CONCLUSIONS
  Both CYP2C19*2 and *17 were common in a New Zealand ACS population, with CYP2C19*2 observed in almost half the Maori and Pacific Island patients. CYP2C19*2, diabetes and clopidogrel dose were independent contributors to on-treatment platelet reactivity.
authors.affiliation: Wellington Cardiovascular Research Group, Wellington Hospital, Wellington, New Zealand.|Department of Surgery and Anaesthesia, University of Otago, Wellington, New Zealand.
authors.forename: P D
authors.initials: PD
authors.lastname: Larsen
authors.affiliation: Wellington Cardiovascular Research Group, Wellington Hospital, Wellington, New Zealand.|School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
authors.forename: L R
authors.initials: LR
authors.lastname: Johnston
authors.affiliation: Wellington Cardiovascular Research Group, Wellington Hospital, Wellington, New Zealand.|School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
authors.forename: A
authors.initials: A
authors.lastname: Holley
authors.affiliation: School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
authors.forename: A C
authors.initials: AC
authors.lastname: La Flamme
authors.affiliation: Carney Centre for Pharmacogenomics, University of Otago, Christchurch, New Zealand.
authors.forename: L
authors.initials: L
authors.lastname: Smyth
authors.affiliation: Carney Centre for Pharmacogenomics, University of Otago, Christchurch, New Zealand.
authors.forename: E W
authors.initials: EW
authors.lastname: Chua
authors.affiliation: Carney Centre for Pharmacogenomics, University of Otago, Christchurch, New Zealand.
authors.forename: M A
authors.initials: MA
authors.lastname: Kennedy
authors.affiliation: Wellington Cardiovascular Research Group, Wellington Hospital, Wellington, New Zealand.|Cardiology Department, Wellington Hospital, Wellington, New Zealand.
authors.forename: S A
authors.initials: SA
authors.lastname: Harding
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D000483:Alleles; D001792:Blood Platelets / Q000473:pathology*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009520:New Zealand / Q000453:epidemiology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D015995:Prevalence; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index
chemical_list: D010975:Platelet Aggregation Inhibitors; D065731:Cytochrome P-450 CYP2C19
keywords: acute coronary syndrome; ethnicity; platelet activation/drug effect; ticlopidine/*analogue and derivative; ticlopidine/therapeutic use