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Pharmacogenomics. 2012 Mar;13(4):407-18. doi: 10.2217/pgs.11.164. Epub 2012 Feb 13.

Predicting warfarin dosage in European-Americans and African-Americans using DNA samples linked to an electronic health record.

Author information

1
Department of Medicine, Vanderbilt University in Nashville, TN 37232, USA.

Abstract

AIM:

Warfarin pharmacogenomic algorithms reduce dosing error, but perform poorly in non-European-Americans. Electronic health record (EHR) systems linked to biobanks may allow for pharmacogenomic analysis, but they have not yet been used for this purpose.

PATIENTS & METHODS:

We used BioVU, the Vanderbilt EHR-linked DNA repository, to identify European-Americans (n = 1022) and African-Americans (n = 145) on stable warfarin therapy and evaluated the effect of 15 pharmacogenetic variants on stable warfarin dose.

RESULTS:

Associations between variants in VKORC1, CYP2C9 and CYP4F2 with weekly dose were observed in European-Americans as well as additional variants in CYP2C9 and CALU in African-Americans. Compared with traditional 5 mg/day dosing, implementing the US FDA recommendations or the International Warfarin Pharmacogenomics Consortium (IWPC) algorithm reduced error in weekly dose in European-Americans (13.5-12.4 and 9.5 mg/week, respectively) but less so in African-Americans (15.2-15.0 and 13.8 mg/week, respectively). By further incorporating associated variants specific for European-Americans and African-Americans in an expanded algorithm, dose-prediction error reduced to 9.1 mg/week (95% CI: 8.4-9.6) in European-Americans and 12.4 mg/week (95% CI: 10.0-13.2) in African-Americans. The expanded algorithm explained 41 and 53% of dose variation in African-Americans and European-Americans, respectively, compared with 29 and 50%, respectively, for the IWPC algorithm. Implementing these predictions via dispensable pill regimens similarly reduced dosing error.

CONCLUSION:

These results validate EHR-linked DNA biorepositories as real-world resources for pharmacogenomic validation and discovery.

PMID:
22329724
PMCID:
PMC3361510
DOI:
10.2217/pgs.11.164
[Indexed for MEDLINE]
Free PMC Article

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