Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, Illinois, USA.
Clin Pharmacol Ther. 2010 Apr;87(4):459-64. doi: 10.1038/clpt.2009.223. Epub 2010 Jan 13.
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 CYP2C98 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 CYP2C95, *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.
本研究旨在确定在非裔美国人患者中，维生素 K 氧化还原酶复合物亚单位 1（VKORC1）、细胞色素 P450 2C9（CYP2C9）、CYP4F2 或载脂蛋白 E（APOE）多态性是否会导致华法林维持剂量的变异性超出 CYP2C92 和 3 等位基因和 VKORC1-1639G>A 基因型的影响。在 226 名非裔美国人患者队列中，具有 CYP2C98 等位基因（34（30-47）mg；P=0.023）和 CYP2C92、*3、*5、*6 或 11 等位基因（33（28-40）mg）的患者每周华法林剂量需求较低与 CYP2C91/1 基因型（43（35-56）mg）相比。CYP2C9 等位基因、VKORC1-1639G>A 基因型和临床变量的组合解释了华法林剂量需求的 36%的个体间变异性。相比之下，不包含 CYP2C95、*6、*8 和 *11 等位基因的模型解释了剂量变异性的 30%。没有其他 VKORC1、CYP4F2 或 APOE 多态性导致变异。包含其他 CYP2C9 变体可能会提高华法林给药算法对非裔美国人的预测能力。
