1 Chapman University School of Pharmacy, Irvine, CA, USA.
2 Medical Communications department, Los Angeles, CA, USA.
J Cardiovasc Pharmacol Ther. 2019 Nov;24(6):521-533. doi: 10.1177/1074248419843530. Epub 2019 May 7.
Many warfarin-related genotypes have shown to impact the average daily warfarin (ADW) dose requirements; however, information in non-Caucasian populations is limited.
To identify the frequencies of 4 warfarin-related gene polymorphisms in an ethnically diverse patient population and to examine their impact with other clinical variables on ADW dose requirements.
Patients were recruited from 2 anticoagulation clinics in the Los Angeles area. Blood samples were collected and genotyped for vitamin K epoxide reductase (VKORC1), CYP2C92, CYP2C93, and CYP4F2 after informed consent. Charts were reviewed to collect demographic, clinical, and warfarin dosing data.
A total of 291 patients were included (120 Caucasians, 127 Hispanics, and 44 Asians). In patients with wild-type genotypes for VKORC1, CYP2C92, CYP2C93, and CYP4F2, the highest warfarin requirement was found in Caucasians, lower in Hispanics, and lowest in Asians. Homozygous VKORC1 variant carriers were detected in 15%, 15%, and 79% in Caucasians, Hispanics, and Asians, respectively. Progressive lowering of ADW doses were associated with each VKORC1 variant in Caucasians and Hispanics, but the results in wild-type/ heterozygote Asians were unclear. CYP2C9 variants were associated with lower ADW doses; frequencies of CYP2C92 and CYP2C93 mutations were higher in Caucasians than in Hispanics but rare to none in Asians. The frequencies of CYP4F2 variant were similar across all ethnicities, but their impact on warfarin dose requirement were insignificant. Clinical factors such as age, body surface area, history of coronary artery disease, deep vein thrombosis or atrial fibrillation, and concomitant amiodarone or HMG-CoA reductase inhibitors had varying impact on the ADW requirements in the ethnicities studied.
Our study demonstrated differences among 3 ethnic groups in terms of ADW dose requirements and the impact of associated clinical variables. The results suggest that a single model for all ethnicities may not provide the best performance in predicting warfarin dose requirements.
许多华法林相关基因型已被证明会影响平均每日华法林（ADW）剂量需求；然而，非白种人群的信息有限。
确定在种族多样化的患者群体中 4 种华法林相关基因多态性的频率，并研究它们与其他临床变量对 ADW 剂量需求的影响。
从洛杉矶地区的 2 个抗凝诊所招募患者。采集血样并进行维生素 K 环氧化物还原酶（VKORC1）、CYP2C92、CYP2C93 和 CYP4F2 的基因分型，在获得知情同意后。查阅图表以收集人口统计学、临床和华法林剂量数据。
共纳入 291 例患者（120 例白种人、127 例西班牙裔和 44 例亚洲人）。在 VKORC1、CYP2C92、CYP2C93 和 CYP4F2 野生型基因型的患者中，华法林需求量最高的是白种人，其次是西班牙裔，最低的是亚洲人。VKORC1 变体纯合子携带者分别在白种人、西班牙裔和亚洲人中检出 15%、15%和 79%。在白种人和西班牙裔中，每个 VKORC1 变体与逐渐降低的 ADW 剂量相关，但在野生型/杂合子亚洲人中结果并不明确。CYP2C9 变体与较低的 ADW 剂量相关；CYP2C92 和 CYP2C93 突变在白种人中的频率高于西班牙裔，但在亚洲人中很少见或不存在。CYP4F2 变体在所有种族中的频率相似，但对华法林剂量需求的影响并不显著。年龄、体表面积、冠心病、深静脉血栓或心房颤动病史以及同时使用胺碘酮或 HMG-CoA 还原酶抑制剂等临床因素对所研究种族的 ADW 需求有不同的影响。
我们的研究表明，3 个种族在 ADW 剂量需求方面存在差异，以及相关临床变量的影响。结果表明，针对所有种族的单一模型可能无法在预测华法林剂量需求方面提供最佳性能。
