Predicting clopidogrel response using DNA samples linked to an electronic health record

Delaney, J. T., Ramirez, A. H., Bowton, E., Pulley, J. M., Basford, M. A., Schildcrout, J. S., Shi, Y., Zink, R., Oetjens, M., Xu, H., Cleator, J. H., Jahangir, E., Ritchie, M. D., Masys, D. R., Roden, D. M., Crawford, D. C. and Denny, J. C. (2012) Predicting clopidogrel response using DNA samples linked to an electronic health record. Clinical Pharmacology and Therapeutics, 91 2: 257-263. doi:10.1038/clpt.2011.221


Author Delaney, J. T.
Ramirez, A. H.
Bowton, E.
Pulley, J. M.
Basford, M. A.
Schildcrout, J. S.
Shi, Y.
Zink, R.
Oetjens, M.
Xu, H.
Cleator, J. H.
Jahangir, E.
Ritchie, M. D.
Masys, D. R.
Roden, D. M.
Crawford, D. C.
Denny, J. C.
Title Predicting clopidogrel response using DNA samples linked to an electronic health record
Journal name Clinical Pharmacology and Therapeutics   Check publisher's open access policy
ISSN 0009-9236
1532-6535
Publication date 2012-02
Year available 2011
Sub-type Article (original research)
DOI 10.1038/clpt.2011.221
Open Access Status Not yet assessed
Volume 91
Issue 2
Start page 257
End page 263
Total pages 7
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Formatted abstract
Variants in ABCB1 and CYP2C19 have been identified as predictors of cardiac events during clopidogrel therapy initiated after myocardial infarction (MI) or percutaneous coronary intervention (PCI). In addition, PON1 has recently been associated with stent thrombosis. The reported effects of these variants have not yet been replicated in a real-world setting. We used BioVU, the Vanderbilt DNA repository linked to de-identified electronic health records (EHRs), to find data on patients who were on clopidogrel treatment after an MI and/or a PCI; among these, we identified those who had experienced one or more recurrent cardiac events while on treatment (cases, n = 225) and those who had not experienced any cardiac event while on treatment (controls, n = 468). We found that CYP2C19*2 (hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.16-2.06, P = 0.003) and ABCB1 (HR 1.28, 95% CI 1.04-1.57, P = 0.018), but not PON1 (HR 0.91, 95% CI 0.73-1.12, P = 0.370), were associated with recurrent events. In this population, genetic signals for clopidogrel resistance in ABCB1 and CYP2C19 were replicated, supporting the use of EHRs for pharmacogenomic studies. Our data do not show an association between PON1 and recurrent cardiovascular events.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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