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Lookup NU author(s): Professor Farhad Kamali
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Warfarin-dosing algorithms incorporating CYP2C9 and VKORC1 –1639G>A improve dose prediction compared with algorithms based solely on clinical and demographic factors. However, these algorithms better capture dose variability among whites than Asians or blacks. Herein, we evaluate whether other VKORC1 polymorphisms and haplotypes explain additional variation in warfarin dose beyond that explained by VKORC1 –1639G>A among Asians (n = 1103), blacks (n = 670), and whites (n = 3113). Participants were recruited from 11 countries as part of the International Warfarin Pharmacogenetics Consortium effort. Evaluation of the effects of individual VKORC1 single nucleotide polymorphisms (SNPs) and haplotypes on warfarin dose used both univariate and multi variable linear regression. VKORC1 –1639G>A and 1173C>T individually explained the greatest variance in dose in all 3 racial groups. Incorporation of additional VKORC1 SNPs or haplotypes did not further improve dose prediction. VKORC1 explained greater variability in dose among whites than blacks and Asians. Differences in the percentage of variance in dose explained by VKORC1 across race were largely accounted for by the frequency of the –1639A (or 1173T) allele. Thus, clinicians should recognize that, although at a population level, the contribution of VKORC1 toward dose requirements is higher in whites than in nonwhites; genotype predicts similar dose requirements across racial groups.
Author(s): Limdi NA, Wadelius M, Cavallari L, Eriksson N, Crawford DC, Lee MT, Chen CH, Motsinger-Reif A, Sagreiya H, Liu N, Wu AH, Gage BF, Jorgensen A, Pirmohamed M, Shin JG, Sarez-Kurtz G, Kimmel SE, Johnson JA, Klein TE, Wagner MJ, on behalf of the International Warfarin Pharmacogenetics Consortium
Publication type: Article
Publication status: Published
Journal: Blood
Year: 2010
Volume: 115
Issue: 18
Pages: 3827-3834
Print publication date: 04/03/2010
ISSN (print): 0006-4971
ISSN (electronic): 1528-0020
Publisher: American Society of Hematology
URL: http://dx.doi.org/10.1182/blood-2009-12-255992
DOI: 10.1182/blood-2009-12-255992
Notes: Prof. F. Kamali (Institute of Cellular Medicine, Newcastle University) is a member of the International Warfarin Pharmacogenetics Consortium
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