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Association Between CYP2C19 * 17 Alleles and pH Probe Testing Outcomes in Children With Symptomatic Gastroesophageal Reflux
Author(s) -
Franciosi James P.,
Mougey Edward B.,
Williams Andre,
GomezSuarez Roberto A.,
Thomas Cameron,
Creech Christa L.,
George Katherine,
Corao Diana,
Lima John J.
Publication year - 2018
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.977
Subject(s) - cyp2c19 , gerd , allele , medicine , reflux , proton pump inhibitor , dosing , gastroenterology , genotype , cohort , retrospective cohort study , confounding , disease , genetics , biology , gene , cytochrome p450 , metabolism
Abstract 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.