一种 PPI 并非适合所有人——Barrett 食管患者中 CYP2C19 表型的患病率
One PPI may not fit all-prevalence of CYP2C19 phenotypes in patients with Barrett's esophagus.
作者
作者单位
- Department of Surgery, College of Medicine Jacksonville, University of Florida, Jacksonville, FL, USA. keounapather@gmail.com.
- Department of Surgery, College of Medicine Jacksonville, University of Florida, Jacksonville, FL, USA.
- Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, FL, USA.
摘要
中文
Barrett 食管(BE)与长期胃食管反流病相关,可进展为食管腺癌。BE 主要采用质子泵抑制剂(PPI)治疗,PPI 经细胞色素 P450 2C19(CYP2C19)代谢。CYP2C19 多态性影响 PPI 血浆浓度,按代谢能力分为弱代谢型(PM)、中间代谢型(IM)、正常代谢型(NM)、快速代谢型(RM)和超快速代谢型(UM)。本研究评估了 BE 合并食管裂孔疝(HH)患者中 CYP2C19 表型的患病率。本研究为单中心、接受药物治疗且已行 CYP2C19 基因检测的成人 BE 患者的回顾性分析。按 HH 大小(小、中、大)分组,并按预期 PPI 剂量调整需求将 CYP2C19 表型分为:PM/IM、NM、RM/UM。应用描述性统计和多因素分析确定与 RM/UM 相关的因素。共纳入 97 例患者(女性 58%,中位年龄 61 岁,平均 BMI 27.5),CYP2C19 表型分布为:PM/IM 占 32%(95% CI 0.27-0.41),NM 占 37%(95% CI 0.27-0.47),RM/UM 占 31%(95% CI 0.22-0.40)。59 例存在 HH。值得注意的是,17% 的 RM/UM 患者合并严重的糜烂性食管炎(LA 分级 C/D)。亚组分析显示,无 HH 患者中 RM/UM 的患病率(53%)较 PM/IM/NM(33%)有升高趋势(p = 0.06)。HH 在 PM/IM/NM 中更常见(67%),而 RM/UM 中较少(47%,p = 0.06)。多因素分析显示该趋势持续,RM/UM 患者中 HH 存在率较低(OR 0.43, 95% CI 0.18-1.03)。BE 患者中 RM/UM 表型患病率有升高趋势。RM/UM 表型患者可能受益于 PPI 剂量优化。鉴于食管腺癌预后差且与 BE 关系密切,评估 CYP2C19 表型以优化 PPI 剂量及疗效可能具有重要的公共卫生意义,尚需更多前瞻性研究。
English
Barrett's esophagus (BE) is associated with longstanding gastroesophageal reflux disease and can progress to esophageal adenocarcinoma. BE is primarily managed with proton pump inhibitors (PPIs), which are metabolized by cytochrome P450 2C19 (CYP2C19). CYP2C19 polymorphisms affect PPI plasma levels, which are categorized as poor (PM), intermediate (IM), normal (NM), rapid (RM), and ultra-rapid (UM) metabolizers. This study assessed the prevalence of CYP2C19 phenotypes in patients with BE and concomitant hiatal hernias (HH). This was a single-institution retrospective review of medically-managed adult BE patients with CYP2C19 genotyping. Patients were grouped by HH size (small, medium, or large). CYP2C19 phenotypes were stratified by genotype as: PM/IM, NM, and RM/UM based on anticipated need for PPI dose adjustment. Descriptive statistics and a multivariable analysis to determine factors associated with RM/UM were used. A total of 97 patients (58% female, median age 61, mean BMI 27.5) were included, and CYP2C19 phenotypes were PM/IM (32%, 95% CI 0.27-0.41), NM (37%, 95% CI 0.27-0.47), and RM/UM (31%, 95% CI 0.22-0.40). HHs were present in 59 patients. Notably, 17% of RM/UM patients had concomitant severe erosive esophagitis, LA grade C/D. On sub-analysis, there was a trend toward higher prevalence of RM/UMs(53%) compared with PM/IM/NM (33%, p = 0.06) in patients who did not have a HH. The presence of HHs tended to be more frequent in the PM/IM/NMs (67%) compared with RM/UMs (47%, p = 0.06). On multivariable analysis, this trend persisted with HHs being less present with RM/UMs (OR 0.43, 95% CI 0.18-1.03). There is a trend toward high prevalence of the RM/UM phenotype in patients with BE. Patients with RM/UM phenotype could benefit from PPI dose optimization. Given the poor survival associated with esophageal adenocarcinoma and its association with BE, assessing CYP2C19 phenotype to optimize PPI dosage and effectiveness could have significant public health implications, and additional prospective studies are needed.
分类与指标
- 研究类型
- 临床研究
- 病种
- 食管癌
- JCR 分区
- Q1
- 影响因子
- 11.8
- 新锐分区
- 1区