Prevalence and significance of CYP2C19*2 and CYP2C19*17 alleles in a New Zealand acute coronary syndrome population

P. D. Larsen, L. R. Johnston, A. Holley, A. C. La Flamme, L. Smyth, Eng Wee Chua, M. A. Kennedy, S. A. Harding

Research output: Contribution to journalArticle

4 Citations (Scopus)

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. Aim: 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.

Original languageEnglish
Pages (from-to)537-545
Number of pages9
JournalInternal Medicine Journal
Volume45
Issue number5
DOIs
Publication statusPublished - 1 May 2015
Externally publishedYes

Fingerprint

Acute Coronary Syndrome
New Zealand
Alleles
clopidogrel
Population
Blood Platelets
Pacific Islands
Confidence Intervals
Cytochrome P-450 CYP2C19
Point-of-Care Systems
Therapeutics
Real-Time Polymerase Chain Reaction
Multivariate Analysis

Keywords

  • Acute coronary syndrome
  • analogue and derivative
  • Ethnicity
  • Platelet activation/drug effect
  • Ticlopidine/
  • Ticlopidine/therapeutic use

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Prevalence and significance of CYP2C19*2 and CYP2C19*17 alleles in a New Zealand acute coronary syndrome population. / Larsen, P. D.; Johnston, L. R.; Holley, A.; La Flamme, A. C.; Smyth, L.; Chua, Eng Wee; Kennedy, M. A.; Harding, S. A.

In: Internal Medicine Journal, Vol. 45, No. 5, 01.05.2015, p. 537-545.

Research output: Contribution to journalArticle

Larsen, PD, Johnston, LR, Holley, A, La Flamme, AC, Smyth, L, Chua, EW, Kennedy, MA & Harding, SA 2015, 'Prevalence and significance of CYP2C19*2 and CYP2C19*17 alleles in a New Zealand acute coronary syndrome population', Internal Medicine Journal, vol. 45, no. 5, pp. 537-545. https://doi.org/10.1111/imj.12698
Larsen, P. D. ; Johnston, L. R. ; Holley, A. ; La Flamme, A. C. ; Smyth, L. ; Chua, Eng Wee ; Kennedy, M. A. ; Harding, S. A. / Prevalence and significance of CYP2C19*2 and CYP2C19*17 alleles in a New Zealand acute coronary syndrome population. In: Internal Medicine Journal. 2015 ; Vol. 45, No. 5. pp. 537-545.
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AU - Larsen, P. D.

AU - Johnston, L. R.

AU - Holley, A.

AU - La Flamme, A. C.

AU - Smyth, L.

AU - Chua, Eng Wee

AU - Kennedy, M. A.

AU - Harding, S. A.

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N2 - 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. Aim: 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.

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