A simulation of warfarin maintenance dose requirement using a pharmacogenetic algorithm in an ethnically diverse cohort

Personalized Medicine
Patrick GladdingHarvey White

Abstract

Patient demographics and variant alleles in the CYP2C9 and VKORC1 genes account for 50% of the population variability in warfarin maintenance doses. These variant alleles occur in varying frequencies between racial groups and contribute to differences in mean dose requirements between these groups. We used a pharmacogenetic simulation to estimate warfarin maintenance doses in an ethnically diverse cohort. In total, 366 individuals with coronary disease, of mixed South Pacific and European ethnicity, were genotyped for the CYP2C9*2 (rs1799853), *3 (rs1057910) and the VKORC1*2 haplotype, -1639 G>A, (rs9923231). The cohort contained New Zealand Europeans (n = 287), Mãori (n = 49), Pacific Islanders (n = 21) and Chinese subjects (n = 9). SNPs were genotyped using the Sequenom (CA, USA) mass spectrometer. Body surface area, age, smoking status and genotype were entered into a modified pharmacogenetic algorithm with a target international normalized ratio of 2.5. Bootstrap analysis using the @RISK software v5.0, (Palisade Co., NY, USA) was performed to simulate a population of 1000 for each ethnic group. Simulated warfarin doses were lower in Chinese subjects than New Zealand Europeans (Δ1.39 mg; 95% CI: 0.4-2.4; p = 0.006) owing to ...Continue Reading

References

Aug 1, 1996·Pharmacogenetics·T H Sullivan-KloseJ A Goldstein
May 3, 2001·The New England Journal of Medicine·R S Schwartz
Mar 7, 2003·Clinical Pharmacology and Therapeutics·Harumi TakahashiHirotoshi Echizen
Dec 24, 2003·Thrombosis and Haemostasis·Brian F GageHoward L McLeod
Feb 5, 2004·Journal of Thrombosis and Thrombolysis·Brian F Gage, Charles S Eby
Sep 17, 2004·Clinical Pharmacology and Therapeutics·Feng ZhaoSoo Chin Lee
May 11, 2005·The Pharmacogenomics Journal·M WadeliusP Deloukas
Jan 25, 2006·Journal of Human Genetics·Taisei MushirodaYusuke Nakamura
Nov 9, 2007·Circulation·Jeffrey L AndersonUNKNOWN Couma-Gen Investigators
Feb 6, 2008·Blood·Michael D CaldwellJames K Burmester
Feb 29, 2008·Clinical Pharmacology and Therapeutics·B F GageH L McLeod
Feb 21, 2009·The New England Journal of Medicine·UNKNOWN International Warfarin Pharmacogenetics ConsortiumJ A Johnson
Sep 1, 2009·The New England Journal of Medicine·Stuart J ConnollyUNKNOWN RE-LY Steering Committee and Investigators

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Citations

Jul 1, 2010·Personalized Medicine·Patrick GladdingRalph Stewart
Oct 26, 2011·British Journal of Clinical Pharmacology·May P S Lam, Bernard M Y Cheung

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Methods Mentioned

BETA
genotyping

Software Mentioned

RISK Excel
Sequenom
StatTools
DecisionTools Suite

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