Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Mol Diagn Ther. 2012 Aug 1;16(4):223-34. doi: 10.1007/BF03262211.
The main therapeutic agent for gastroesophageal reflux disease (GERD) is a proton pump inhibitor (PPI). Plasma levels and the acid inhibitory effect of PPIs depend on the activity of cytochrome P450 (CYP) 2C19, which is polymorphic. Genotypes of CYP2C19 are classified into three groups: rapid metabolizers (RMs: *1/*1), intermediate metabolizers (IMs: *1/*X), and poor metabolizers (PMs: *X/*X), where 1 and X represent the wild type and the mutant allele, respectively. RMs include ultra-rapid metabolizers, who possess the CYP2C1917 allele. The pharmacokinetics and pharmacodynamics of PPIs differ among different CYP2C19 genotype groups. Plasma PPI levels and intragastric pH values during PPI treatment are lowest in the RM group, intermediate in the IM group, and highest in the PM group. These CYP2C19-genotype-dependent differences in the pharmacokinetics and pharmacodynamics of PPIs influence the healing and recurrence of GERD during PPI treatment, suggesting the need for CYP2C19 genotype-based tailored therapy for GERD. CYP2C19 pharmacogenetics should be taken into consideration for the personalization of PPI-based therapy. However, the clinical usefulness of CYP2C19 genotype testing in GERD therapy should be verified in clinical studies.
胃食管反流病（GERD）的主要治疗药物是质子泵抑制剂（PPI）。PPI 的血浆水平和抑酸作用取决于细胞色素 P450（CYP）2C19 的活性，而 CYP2C19 具有多态性。CYP2C19 基因型分为三组：快速代谢者（RMs：*1/*1）、中间代谢者（IMs：*1/*X）和弱代谢者（PMs：X/X），其中1 和 X 分别代表野生型和突变型等位基因。RMs 包括具有 CYP2C1917 等位基因的超快代谢者。不同 CYP2C19 基因型组的 PPI 药代动力学和药效动力学存在差异。在 PPI 治疗期间，PPIs 的血浆水平和胃内 pH 值在 RM 组最低，在 IM 组中等，在 PM 组最高。这些 CYP2C19 基因型依赖性的 PPI 药代动力学和药效动力学差异影响 GERD 在 PPI 治疗期间的愈合和复发，表明需要针对 GERD 进行基于 CYP2C19 基因型的个体化治疗。CYP2C19 药物遗传学应考虑用于基于 PPI 的个体化治疗。然而，CYP2C19 基因型检测在 GERD 治疗中的临床实用性应在临床研究中得到验证。
