Document Detail


Effect of genetic variants, especially CYP2C9 and VKORC1, on the pharmacology of warfarin.
MedLine Citation:
PMID:  23041981     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The genes encoding the cytochrome P450 2C9 enzyme (CYP2C9) and vitamin K-epoxide reductase complex unit 1 (VKORC1) are major determinants of anticoagulant response to warfarin. Together with patient demographics and clinical information, they account for approximately one-half of the warfarin dose variance in individuals of European descent. Recent prospective and randomized controlled trial data support pharmacogenetic guidance with their use in warfarin dose initiation and titration. Benefits from pharmacogenetics-guided warfarin dosing have been reported to extend beyond the period of initial dosing, with supportive data indicating benefits to at least 3 months. The genetic effects of VKORC1 and CYP2C9 in African and Asian populations are concordant with those in individuals of European ancestry; however, frequency distribution of allelic variants can vary considerably between major populations. Future randomized controlled trials in multiethnic settings using population-specific dosing algorithms will allow us to further ascertain the generalizability and cost-effectiveness of pharmacogenetics-guided warfarin therapy. Additional genome-wide association studies may help us to improve and refine dosing algorithms and potentially identify novel biological pathways.
Authors:
Erik Fung; Nikolaos A Patsopoulos; Steven M Belknap; Daniel J O'Rourke; John F Robb; Jeffrey L Anderson; Nicholas W Shworak; Jason H Moore
Publication Detail:
Type:  Journal Article; Review     Date:  2012-10-06
Journal Detail:
Title:  Seminars in thrombosis and hemostasis     Volume:  38     ISSN:  1098-9064     ISO Abbreviation:  Semin. Thromb. Hemost.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-06     Completed Date:  2013-06-27     Revised Date:  2014-08-19    
Medline Journal Info:
Nlm Unique ID:  0431155     Medline TA:  Semin Thromb Hemost     Country:  United States    
Other Details:
Languages:  eng     Pagination:  893-904     Citation Subset:  IM    
Copyright Information:
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Anticoagulants / adverse effects*,  pharmacology
Aryl Hydrocarbon Hydroxylases / genetics*,  metabolism
Genetic Variation
Genotype
Humans
International Normalized Ratio
Mixed Function Oxygenases / genetics*,  metabolism
Vitamin K Epoxide Reductases
Warfarin / adverse effects*,  pharmacology
Grant Support
ID/Acronym/Agency:
P20 GM103534/GM/NIGMS NIH HHS; P20 RR024475/RR/NCRR NIH HHS; P30 CA023108/CA/NCI NIH HHS; P50 HL081009/HL/NHLBI NIH HHS; R01 AG023590/AG/NIA NIH HHS; R01 HL079104/HL/NHLBI NIH HHS; R01 LM010098/LM/NLM NIH HHS
Chemical
Reg. No./Substance:
0/Anticoagulants; 5Q7ZVV76EI/Warfarin; EC 1.-/Mixed Function Oxygenases; EC 1.1.4.1/VKORC1 protein, human; EC 1.1.4.1/Vitamin K Epoxide Reductases; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/CYP2C9 protein, human
Comments/Corrections
Erratum In:
Semin Thromb Hemost. 2013 Feb;39(1):112

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Venous and Arterial Thromboembolic Complications Associated with HIV Infection and Highly Active Ant...
Next Document:  D-Dimer Assays in Diagnosis and Management of Thrombotic and Bleeding Disorders.