Relevance of genetic polymorphisms of the human cytochrome P450 3A4 in rivaroxaban-treated patients
Relevance of genetic polymorphisms of the human cytochrome P450 3A4 in rivaroxaban-treated patients
复制标题
利伐沙班治疗患者中人细胞色素 P450 3A4 遗传多态性的相关性
DOI：
10.55705/cmbr.2021.138880.1003
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Z. Aziziaram
中科院分区：
文献类型：
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作者：
M. Ercisli;Lechun Gao;S. Azeez;R. Hamasalih;Siyan Song;Z. Aziziaram
利伐沙班是一种抗凝血药物，可防止血栓形成。此外，它可以用于预防和治疗血栓性疾病，如心房颤动、心律失常、心脏瓣膜疾病、整形外科手术和血栓形成倾向，以降低血栓形成的风险。各种因素，如年龄，性别，饮食，药物和遗传因素，有效地确定利伐沙班的剂量。药物代谢酶（包括细胞色素P450（CYP 450）酶，尤其是CYP 3A 4）的遗传变异性与利伐沙班反应相关。本研究旨在确定100例阿拉伯裔患者（48.6%为女性）中CYP 3A 4常见多态性的频率及其与利伐沙班应答的相关性。采用PCR-RFLP方法检测CYP 3A 4基因多态性，用SPSS 16统计软件进行t检验。CYP 3A 4 *1B/*1B、CYP 3A 4 *1B/*1A、CYP 3A 4 * 1B/*1C和CYP 3A 4 *1A/*1C的频率分别为67.35%、10.64%、19.12%和2.89%。根据我们的结果，CYP 3A 4 *1B/*1B基因型最常见，携带CYP 3A 4 *1B/*1B等位基因的患者需要的利伐沙班日剂量高于 *1B/*1A、*1B/*1C和 *1A/*1C携带者（9.57 ± 1.54 mg/d，P=0.015）。因此，根据结果，CYP 3A 4基因多态性对维持国际标准化比值（INR）在2-3范围内所需的利伐沙班剂量具有重要影响。
Rivaroxaban is an anticoagulant drug that prevents forming of blood clots. In addition, it can be administered to prevent and treat thrombotic diseases such as atrial fibrillation, cardiac arrhythmia, heart valve disease, orthopedic surgery, and thrombophilia to reduce the risk of thrombosis. Various factors such as age, gender, diet, medications, and genetic factors effectively determine the dose of rivaroxaban. Genetic variability in drug-metabolizing enzymes, including the cytochrome P450 (CYP450) enzymes and especially CYP3A4, has been associated with rivaroxaban response. The current study aimed to identify the frequency of CYP3A4 common polymorphisms, as well as their association with rivaroxaban response in 100 patients of Arab descent (48.6% female). CYP3A4 gene polymorphisms were examined by the PCR-RFLP method, and the findings were analyzed by SPSS 16 software and t-test. The frequency of CYP3A4*1B/*1B, CYP3A4*1B/*1A, CYP3A4*1B/*1C, and CYP3A4*1A/*1C was 67.35%, 10.64%, 19.12% and 2.89%, respectively. According to our results, CYP3A4 *1B/*1B genotype was the most common, and patients with CYP3A4*1B/*1B alleles needed a higher daily dose of rivaroxaban than *1B/*1A, *1B/*1C, and *1A/*1C carriers (9.57 ± 1.54 mg/day, P=0.015). Therefore, according to the results, CYP3A4 gene polymorphism has an important effect on the dose of rivaroxaban required to maintain the International Normalized Ratio (INR) in the range of 2-3.