School of Pharmacy, Department of Pharmaceutical Sciences, University of Puerto Rico, San Juan, Puerto Rico.
Ethn Dis. 2009 Autumn;19(4):390-5.
Polymorphisms in the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genes significantly alter the effective warfarin dose. We determined the frequencies of alleles, single carriers, and double carriers of single nucleotide polymorphisms (SNPs) in the CYP2C9 and VKORC1 genes in a Puerto Rican cohort and gauged the impact of these polymorphisms on warfarin dosage using a published algorithm. A total of 92 DNA samples were genotyped using Luminex x-MAP technology. The polymorphism frequencies were 6.52%, 5.43% and 28.8% for CYP2C9 *2, *3 and VKORC1-1639 C>A polymorphisms, respectively. The prevalence of combinatorial genotypes was 16% for carriers of both the CYP2C9 and VKORC1 polymorphisms, 9% for carriers of CYP2C9 polymorphisms, 35% for carriers of the VKORC1 polymorphism, and the remaining 40% were non-carriers for either gene. Based on a published warfarin dosing algorithm, single, double and triple carriers of functionally deficient polymorphisms predict reductions of 1.0-1.6, 2.0-2.9, and 2.9-3.7 mg/day, respectively, in warfarin dose. Overall, 60% of the population carried at least a single polymorphism predicting deficient warfarin metabolism or responsiveness and 13% were double carriers with polymorphisms in both genes studied. Combinatorial genotyping of CYP2C9 and VKORC1 can allow for individualized dosing of warfarin among patients with gene polymorphisms, potentially reducing the risk of stroke or bleeding.
细胞色素 P450 2C9（CYP2C9）和维生素 K 环氧化物还原酶复合物亚基 1（VKORC1）基因的多态性显著改变了华法林的有效剂量。我们在波多黎各人群中确定了 CYP2C9 和 VKORC1 基因中单核苷酸多态性（SNP）的等位基因、单载体和双载体的频率，并使用已发表的算法评估了这些多态性对华法林剂量的影响。总共使用 Luminex x-MAP 技术对 92 个 DNA 样本进行了基因分型。CYP2C9 * 2、* 3 和 VKORC1-1639 C>A 多态性的多态性频率分别为 6.52%、5.43%和 28.8%。CYP2C9 和 VKORC1 多态性携带者的组合基因型的患病率为 16%，CYP2C9 多态性携带者为 9%，VKORC1 多态性携带者为 35%，其余 40%的人两种基因均非携带者。根据已发表的华法林给药算法，功能缺陷多态性的单、双和三载体预测华法林剂量分别减少 1.0-1.6、2.0-2.9 和 2.9-3.7mg/天。总体而言，60%的人群至少携带一种预测华法林代谢或反应不足的单态多态性，13%的人群是携带两种研究基因多态性的双载体。CYP2C9 和 VKORC1 的组合基因分型可以实现基因多态性患者的华法林个体化给药，潜在降低中风或出血的风险。
