Pharmacogenetics of CYP3A5 in Pediatric Patients With Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is an atopic inflammatory disease with limited treatment options. Though swallowed topical steroids are commonly used, they are not effective in all patients. We investigated the presence of CYP3A4/5 and ABCB1 (P-glycoprotein) mRNA in esophageal tissue and its differential expression by genotype in pediatric patients. Esophageal tissue biopsies were obtained from pediatric patients undergoing standard of care endoscopy. Levels of CYP3A4, CYP3A5, and ABCB1 mRNA were measured using droplet digital PCR and compared across patients with and without EoE. Genotypes for common, clinically relevant CYP3A5 variants were evaluated in a cohort of individuals with and without EoE. Levels of CYP3A4 and ABCB1 in the esophagus were negligible in all patients. CYP3A5 mRNA expression was highest with two wild type alleles (*1/*1) and lowest with no wild type alleles. Further investigation into the function of esophageal CYP3A5 and its ability to metabolize budesonide delivered to the esophagus is warranted.