Association Between CYP2C19*17 Alleles and pH Probe Testing Outcomes in Children With Symptomatic Gastroesophageal Reflux
Association Between CYP2C19*17 Alleles and pH Probe Testing Outcomes in Children With Symptomatic Gastroesophageal Reflux
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DOI：
10.1002/jcph.977
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发表时间：
2018-01-01
影响因子：
2.9
通讯作者：
Lima, John J.
中科院分区：
文献类型：
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作者：
Franciosi, James P.;Mougey, Edward B.;Lima, John J.
食管pH监测仍然是检测胃食管反流病（GERD）的主要诊断工具。质子泵抑制剂（PPI）药物难治性GERD可能与CYP 2C 19变体相关。目前儿童PPI给药实践未考虑CYP 2C 19等位基因变异，这可能导致剂量不足，随后导致PPI治疗失败的误解。我们假设pH探针酸暴露结果与临床关注GERD的儿童中的CYP 2C 19 *17等位基因相关。我们确定了一个由74名儿童（年龄范围0.71-17.1岁，平均8.5岁，SD 4.6）组成的回顾性队列，这些儿童在接受PPI治疗时也接受了食管pH值检测。对这些个体进行常见CYP 2C 19等位基因的基因分型，并将其二分为CYP 2C 19 *17等位基因携带者，而没有相应的功能等位基因丧失，作为病例与对照。研究了pH探针酸暴露结果与CYP 2C 19 *17等位基因之间的相关性。与对照组相比，携带CYP 2C 19 *17等位基因而没有相应功能丧失等位基因的儿童表现出具有统计学意义的pH < 4的时间更长（76.46 vs 33.47分钟，P = .03）; pH < 4.0的时间百分比更高（5.71 vs 2.67分钟，P=.04）。使用以测试持续时间、PPI剂量和种族作为混杂变量的多元回归建模，这些发现仍然具有统计学意义。在pH探针检测之前，通过CYP 2C 19基因型指导给药，可以更好地优化 *17等位基因儿童的PPI治疗。
Esophageal pH monitoring remains a primary diagnostic tool for detecting gastroesophageal reflux disease (GERD). GERD that is refractory to proton pump inhibitor (PPI) medications may be related to CYP2C19 variants. Current PPI dosing practices in children do not take into account CYP2C19 allelic variants, which may lead to underdosing and subsequently to a misperception of PPI therapy failure. We hypothesized that pH probe acid exposure outcomes associate with CYP2C19*17 alleles among children with clinical concern for GERD. We identified a retrospective cohort of 74 children (age range 0.71-17.1 years, mean 8.5, SD 4.6) with stored endoscopic tissue samples and who had also undergone esophageal pH testing while on PPI therapy. These individuals were genotyped for common CYP2C19 alleles and were dichotomized to either CYP2C19*17 allelic carriers without corresponding loss of function alleles as cases vs controls. Associations between pH probe acid exposure outcomes and CYP2C19*17 alleles were investigated. Compared to controls, children who carry CYP2C19*17 alleles without corresponding loss-of-function alleles demonstrated statistically significant longer times with pH < 4 (76.46 vs 33.47 minutes, P = .03); and higher percent of time with pH < 4.0 (5.71 vs 2.67 minutes, P=.04). These findings remained statistically significant using multiple-regression modeling with test duration, PPI dose, and race as confounding variables. PPI therapy in children with *17 alleles may be better optimized with CYP2C19 genotype-guided dosing prior to pH probe testing.