Effect of cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole
Effect of cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole
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DOI：
10.1067/mcp.2002.127637
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发表时间：
2002-10-01
影响因子：
6.7
通讯作者：
Hanai, H
中科院分区：
文献类型：
--
作者：
Furuta, T;Shirai, N;Hanai, H
背景和目标。兰索拉唑的酸抑制作用取决于细胞色素P450（CYP）2C19基因型的差异。我们评估了兰索拉唑对胃食管反流疾病（GERD）的治疗作用是否取决于与GERD.Methods等级有关的CYP2C19基因型状态。总共有65例GERD患者（A-D级）通过每天口服30 mg口服8周，完成了兰索拉唑的治疗。通过聚合酶链反应限制片段长度多态性分析确定患者的CYP2C19基因型状态。治疗前后，进行食管内窥镜检查。在治疗结束时内窥镜发现的基础上，认为GERD被认为是治愈的。在27例基因型患者中，最后30毫克兰索拉唑剂量后3小时可以确定血浆兰索水平。 GERD的治疗率显着取决于CYP2C19基因型状态以及治疗前GERD等级。纯合广泛，杂合广泛和差的代谢组的治疗率分别为45.8％，67.9％和84.6％。 GERD A级，B级和C级或D级的组的治疗率分别为85.0％，60.0％和45.0％。 CYP2C19的纯合广泛代谢基因型患者的治疗率为C或D级为C或D级非常低（16.7％）。纯合广泛代谢基因型的患者的血浆兰索水平是3组中最低的。 CYP2C19基因型状态以及治疗前的GERD等级是成功或失败使用兰索拉唑治疗GERD的决定因素之一。纯合广泛的代谢基因型的患者的治疗率低似乎是由于这些患者在3种基因型组中具有最低血浆兰索拉唑水平的结果。
Background and objectives. The acid-inhibitory effect of lansoprazole depends on differences in cytochrome P450 (CYP) 2C19 genotypes. We assessed whether therapeutic effects of lansoprazole on gastroesophageal reflux disease (GERD) depended on the CYP2C19 genotype status in relation to the grade of GERD.Methods. A total of 65 patients with GERD (grades A-D) completed treatment with lansoprazole, by taking 30 mg orally once a day for 8 weeks. The CYP2C19 genotype status of patients was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Before and after treatment, esophageal endoscopy was performed. GERD was considered to be cured on the basis of endoscopic findings at the end of treatment. Plasma lansoprazole levels could be determined at 3 hours after the last 30-mg dose of lansoprazole in the 27 genotyped patients.Results. Cure rates for GERD depended significantly on the CYP2C19 genotype status, as well as the grade of GERD before treatment. Cure rates in the homozygous extensive, heterozygous extensive, and poor metabolizer groups were 45.8%, 67.9%, and 84.6%, respectively. Cure rates in the groups with GERD grade A, grade B, and grade C or D were 85.0%, 60.0%, and 45.0%, respectively. The cure rate in patients with the homozygous extensive metabolizer genotype of CYP2C19 with a GERD grade of C or D was very low (16.7%). Plasma lansoprazole levels in patients with the homozygous extensive metabolizer genotype were the lowest of the 3 groups.Conclusions. CYP2C19 genotype status, as well as the grade of GERD before treatment, is one of the determinants for the success or failure of treatment of GERD with lansoprazole. The low cure rate in patients with the homozygous extensive metabolizer genotype appeared to be a result of these patients having the lowest plasma lansoprazole levels among the 3 genotype groups.