Genetic and Clinical Predictors of Warfarin Dose Requirements in African Americans

被引：158

作者：

Cavallari, L. H. ^{[1
]}

Langaee, T. Y. ^{[2
]}

Momary, K. M. ^{[1
]}

Shapiro, N. L. ^{[1
]}

Nutescu, E. A. ^{[1
]}

Coty, W. A. ^{[3
]}

Viana, M. A. G. ^{[4
]}

Patel, S. R. ^{[1
]}

Johnson, J. A. ^{[2
]}

机构：

[1] Univ Illinois, Dept Pharm Practice, Chicago, IL 60607 USA

[2] Univ Florida, Dept Pharmacotherapy & Translat Res, Ctr Pharmacogen, Gainesville, FL USA

[3] Osmetech Mol Diagnost, Pasadena, CA USA

[4] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2010年 / 87卷 / 04期

关键词：

REDUCTASE COMPLEX SUBUNIT-1; GAMMA-GLUTAMYL CARBOXYLASE; CYTOCHROME P4502C9; APOLIPOPROTEIN-E; DOSAGE REQUIREMENTS; EUROPEAN-AMERICANS; ITALIAN POPULATION; VKORC1; HAPLOTYPES; CYP2C9; MAINTENANCE;

D O I：

10.1038/clpt.2009.223

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The objective of this study was to determine whether, in African-American patients, additional vitamin K oxidoreductase complex subunit 1 (VKORC1), cytochrome P450 2C9 (CYP2C9), CYP4F2, or apolipoprotein E (APOE) polymorphisms contribute to variability in the warfarin maintenance dose beyond what is attributable to the CYP2C9*2 and *3 alleles and the VKORC1 -1639G> A genotype. In a cohort of 226 African-American patients, weekly warfarin dose requirements were lower in those with the CYP2C9*8 allele (34 (30-47) mg; P = 0.023) and the CYP2C9 *2, *3, *5, *6, or *11 allele (33 (28-40 mg); P < 0.001) as compared with those with the CYP2C9*1/*1 genotype (43 (35-56) mg). The combination of CYP2C9 alleles, VKORC1-1639G> A genotype, and clinical variables explained 36% of the interpatient variability in warfarin dose requirements. By comparison, a model without the CYP2C9*5, *6, *8, and *11 alleles explained 30% of the variability in dose. No other VKORC1, CYP4F2, or APOE polymorphism contributed to the variance. The inclusion of additional CYP2C9 variants may improve the predictive ability of warfarin dosing algorithms for African Americans.

引用

页码：459 / 464

页数：6

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