September 12, 2019
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Genetic variants affect PPI response in pediatric EoE

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Researchers from Nemours Children’s Health System identified gene variants that influence the efficacy of proton pump inhibitor therapy in children with eosinophilic esophagitis and said their findings could lead to new opportunities for personalized medicine.

“Currently, only 30% to 60% of children respond when treated with PPIs to reduce inflammation from eosinophilic esophagitis,” James P. Franciosi, MD, chief of gastroenterology, hepatology and nutrition for Nemours Children’s Hospital, said in a press release. “Our study found that treatment response is strongly influenced by common genetic variants that affect how the body metabolizes or responds to PPIs. These findings could lead to individualized therapy based on a person’s genetics.”

Researchers collected esophageal tissue biopsies from 92 patients (aged 2 to 16 years) enrolled in a prospective trial of high-dose PPI therapy. They isolated genomic DNA to determine whether genetic variation in the genes for CYP2C19 and STAT6 helped differentiate between patients who did and did not respond to PPIs.

Of the patients enrolled in the study, 57 responded to PPIs (62%) and 35 did not (38%). Among 46 patients who underwent pH probe monitoring, researchers found no association between CYP2C19*17 and reflux.

Infographic detailing the genetic variant that impacts success of PPIs in EoE.
Researchers from Nemours Children’s Health System identified gene variants that influence the efficacy of proton pump inhibitor therapy in children with eosinophilic esophagitis and said their findings could lead to new opportunities for personalized medicine.

In children who received a PPI dose between 1.54 mg/kg and 2.05 mg/kg per day, researchers found that carriage of CYP2C19*17 was associated with PPI-nonresponsive EoE (OR = 7.71; 95% CI, 1.21-49.11).

While carriage of STAT6 allelic variant rs1059513 predicted PPI-responsive EoE (OR = 6.16; 95% CI, 1.44-26.4), another allelic variant of STAT6 — rs324011 — combined with CYP2C19*17 to predict PPI-nonresponsive EoE (OR for rs324011 = 5.56; 95% CI, 1.33-20.72; OR for CYP2C19*17 = 8.19; 95% CI, 1.42-50.57).

Investigators wrote that future research and development of personalized medicine for children with EoE could improve the benefit of therapy and reduce some of the adverse effects.

“Without considering information about a patient’s genetics, clinicians may be prescribing a lower or higher PPI dose than is necessary, which could lead to treatment failure or PPI-associated side effects including upper respiratory and GI tract infections,” Edward B. Mougey, PhD, of Nemours’ Center for Pharmacogenomics and Translational Research, said in the press release. “The general strategy of dose adjustment to compensate for genetic variants of drug-metabolizing enzymes carried by an individual is the cornerstone of precision medicine.” by Alex Young

Disclosures: The authors report no relevant financial disclosures.