Department of Pharmacy Practice, College of Pharmacy, 833 S. Wood St, Chicago, IL 60612, USA.
Blood Cells Mol Dis. 2011 Feb 15;46(2):147-50. doi: 10.1016/j.bcmd.2010.11.005. Epub 2010 Dec 24.
While Hispanics are the largest and most rapidly growing minority population in the United States, they are underrepresented in pharmacogenomic studies with warfarin. We sought to determine the combination of clinical and genetic influences of warfarin dose requirements in Hispanics. In addition, we tested the performance of published warfarin dosing algorithms derived from largely non-Hispanic cohorts in an inner-city U.S. Hispanic population. Genetic samples and clinical data were obtained from 50 Hispanics on a stable dose of warfarin. The contribution of cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex-1 (VKORC1) genotypes and clinical factors to warfarin dose requirements was determined. The correlation between the predicted dose using published algorithms and therapeutic dose was also assessed. Compared to the VKORC1-1639 GG genotype, warfarin dose requirements were 30% and 62% lower with the GA and AA genotypes, respectively (p=0.001). The combination of the VKORC1-1639G>A and CYP2C9 genotypes and clinical factors explained 56% of the inter-patient variability in warfarin dose. Warfarin dose predicted using algorithms derived from mostly non-Hispanic cohorts was significantly correlated with the therapeutic dose in our Hispanic cohort (r(2)=0.43 to 0.49; p<0.001); the predicted dose was within 1.0 mg/day of the therapeutic dose for 40% to 50% of patients. Our data suggest that factors influencing warfarin dose requirements in Hispanic Caucasians are similar to those previously described in European Caucasians and that dosing algorithms derived from non-Hispanic Caucasian cohorts are applicable to Hispanics living in the U.S.
尽管西班牙裔是美国最大和增长最快的少数族裔群体，但他们在华法林的药物基因组学研究中代表性不足。我们旨在确定影响西班牙裔人群华法林剂量需求的临床和遗传因素组合。此外，我们还测试了源自主要非西班牙裔人群的已发表的华法林剂量算法在城市西班牙裔人群中的性能。从稳定剂量服用华法林的 50 名西班牙裔个体中获得了遗传样本和临床数据。确定细胞色素 P450 2C9（CYP2C9）和维生素 K 环氧化物还原酶复合物 1（VKORC1）基因型和临床因素对华法林剂量需求的贡献。还评估了使用已发表算法预测的剂量与治疗剂量之间的相关性。与 VKORC1-1639 GG 基因型相比，GA 和 AA 基因型的华法林剂量需求分别降低了 30%和 62%（p=0.001）。VKORC1-1639G>A 和 CYP2C9 基因型与临床因素的组合解释了华法林剂量个体间变异性的 56%。源自主要非西班牙裔人群的算法预测的华法林剂量与我们西班牙裔人群的治疗剂量显著相关（r(2)=0.43 至 0.49；p<0.001）；对于 40%至 50%的患者，预测剂量与治疗剂量相差 1.0mg/天以内。我们的数据表明，影响西班牙裔白种人华法林剂量需求的因素与以前在欧洲白种人中描述的因素相似，并且源自非西班牙裔白种人群的剂量算法适用于居住在美国的西班牙裔人。
