Pharmacogenomics of Warfarin dose requirements in Hispanics
Pharmacogenomics of Warfarin dose requirements in Hispanics
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DOI：
10.1016/j.bcmd.2010.11.005
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发表时间：
2011-02-15
影响因子：
2.3
通讯作者：
Viana, Marlos A. G.
中科院分区：
文献类型：
--
作者：
Cavallari, Larisa H.;Momary, Kathryn M.;Viana, Marlos A. G.
虽然西班牙裔是美国数量最多、增长最快的少数族裔，但他们在华法林药物基因组学研究中的代表性不足。我们试图确定西班牙裔华法林剂量需求的临床和遗传影响的组合。此外，我们还测试了已发表的华法林剂量算法的性能，该算法源自美国市中心的西班牙裔人群中的大部分非西班牙裔群体。基因样本和临床数据是从 50 名服用稳定剂量华法林的西班牙裔中获得的。确定了细胞色素 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影响。还评估了使用已发布算法的预测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低 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的 56% 患者间差异。使用主要来自非西班牙裔队列的算法预测的华法林剂量与我们的西班牙裔队列中的治疗剂量显着相关（r(2) = 0.43 至 0.49；p
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