Journal article
Genetic and environmental factors determining clinical outcomes and cost of warfarin therapy: A prospective study
AL Jorgensen, S Al-Zubiedi, JE Zhang, A Keniry, A Hanson, DA Hughes, DV Eker, L Stevens, K Hawkins, CH Toh, F Kamali, AK Daly, D Fitzmaurice, A Coffey, PR Williamson, BK Park, P Deloukas, M Pirmohamed
Pharmacogenetics and Genomics | Published : 2009
Abstract
BACKGROUND: In this prospective cohort study, we have undertaken a comprehensive evaluation of clinical parameters along with variation in 29 genes (including CYP2C9 and VKORC1) to identify factors determining interindividual variability in warfarin response. METHODS: Consecutive patients (n=311) were followed up prospectively for 26 weeks. Several outcomes chosen to capture both warfarin efficacy and toxicity were assessed. Univariate and multiple regression analyses were undertaken to assess the combined effect of clinical and genetic factors. RESULTS: CYP2C9 was the most important gene determining initial anticoagulant control, whereas VKORC1 was more important for stable anticoagulation...
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Funding Acknowledgements
[ "The authors acknowledge the UK Department of Health for funding the study. The support of the Wellcome Trust is also acknowledged. The authors thank all the clinicians, nurses and pharmacists who helped us in recruiting patients, and the patients for taking part in the study, and the Roald Dahl Anticoagulant clinic in the Royal Liverpool Hospital. The authors also acknowledge the contribution of Dr Vanessa Martlew (Royal Liverpool Hospital) and Dr Dasgupta (University Hospital Aintree) for patient recruitment. The authors thank Susanna Dodd and Fabio Miyajima, University of Liverpool, for their assistance with the analysis of the cost data.", "The conception and design of the study was undertaken by M.P., D.A.H., A.C., EK., A.D., D.E, P.R.W, B.K.P. and RD. A.L.J. was responsible for monitoring of data (also done by P.R.W), statistical analyses of associations with response to warfarin, and wrote the first draft of the manuscript. J.E.Z. undertook all laboratory analyses of clotting factors and preparation of laboratory samples, while A.K. undertook genotyping, supervised by PD. A.H., D.E., K.H. and L.S. recruited the patients, designed the C.R.E and validated the patient data, while C.H.T facilitated patient identification and quality assurance of the coagulation based laboratory tests. A.C. supervised the DNA extraction. SAX and DA.H. undertook the cost analysis. M.P. is the principal investigator, conceived the design of the study, coordinated the study, was involved in data monitoring and assessment of patients, and co-wrote first draft. All authors were involved in reviewing the manuscript and approved the final version. M.P. acts as guarantor for the study." ]