Prevalence and significance of CYP2C19*2 and CYP2C19*17 alleles in a New Zealand acute coronary syndrome population. Issue 5 (May 2015)

• Record Type: Journal Article
• Authors: Larsen, P. D.; Johnston, L. R.; Holley, A.; La Flamme, A. C.; Smyth, L.; Chua, E. W.; Kennedy, M. A.; Harding, S. A.
• Is Part Of: Internal medicine journal. Volume 45:Issue 5(2015)
• Page Start: 537
• Page End: 545
• Publication Date: 2015-05
• Subjects: Medicine -- Periodicals; 616
• DOI: 10.1111/imj.12698
• Languages: English
• ISSNs: 1444-0903

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="imj12698-sec-0001" sec-type="section"> <title>Background</title> <p>High on‐treatment platelet reactivity has been associated with poor outcomes following acute coronary syndromes (ACS). Both the loss of function <italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*2</italic> allele and the gain of function <italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*17</italic> allele along with a range of clinical characteristics have been associated with variation in the response to clopidogrel.</p> </sec> <sec id="imj12698-sec-1001" sec-type="section"> <title>Aim</title> <p>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.</p> </sec> <sec id="imj12698-sec-0002" sec-type="section"> <title>Methods</title> <p>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 <italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*2</italic> and <italic>*17</italic> alleles were identified using real‐time polymerase chain reaction.</p> </sec> <sec id="imj12698-sec-0003" sec-type="section"> <title>Results</title> <p> <italic>CYP</italic> <italic>2</italic> <italic>C</italic> <italic>19*2</italic> or <italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*17</italic> 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 <italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*2</italic> and 11% (CI 4–19%) <italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*17</italic> compared with 26% (CI 19–32%) and 41% (CI 32–49%) in white people. Carriage of <italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*2</italic> alleles was associated with higher levels of platelet reactivity measured by either assay, but we observed no relationship between platelet reactivity and <italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*17</italic>. In multivariate analysis diabetes, clopidogrel dose and <italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*2</italic> status were all significant independent predictors of platelet reactivity.</p> </sec> <sec id="imj12698-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Both <italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*2</italic> and <italic>*17</italic> were common in a New Zealand ACS population, with <italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*2</italic> observed in almost half the Maori and Pacific Island patients. <italic>CYP</italic><italic>2</italic><italic>C</italic><italic>19*2</italic>, diabetes and clopidogrel dose were independent contributors to on‐treatment platelet reactivity.</p> </sec> </abstract>