STAT6 Variants Associate With Relapse of Eosinophilic Esophagitis in Patients Receiving Long-Term Proton Pump Inhibitor Therapy.

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Variants in STAT6 associate with a poor initial response, based on histologic features, to proton pump inhibitor (PPI) therapy in pediatric patients with eosinophilic esophagitis (EoE). We investigated whether these genetic variants associate with a poor long-term response in children with EoE who initially responded to PPI therapy.We performed a prospective, longitudinal cohort study of children 2-16 years old who met the diagnostic criteria for EoE (≥ 15 eosinophils/high-power field [eos/hpf]), responded to 8 weeks of treatment with 2 mg/kg/day PPI (< 15 eos/hpf), and whose dose was then reduced to 1 mg/kg/day PPI (maintenance therapy) for 1 year at which point biopsies were collected by endoscopy. Genomic DNA was isolated from formalin-fixed paraffin-embedded biopsy tissue and genotyped for variants of STAT6. Remission of inflammation was assessed when biopsies reached thresholds of < 15 eos/hpf and ≤ 5 eos/hpf.Among 73 patients who received 1 mg/kg/day PPI maintenance therapy for 1 year, 13 patients (18%) had 6-14 eos/hpf , 36 patients (49%) had ≤5 eos/hpf, and 24 patients (33%) relapsed to EoE (≥ 15 eos/hpf). Carriage of any of 3 variants in STAT6 in linkage disequilibrium (r2 ≥ 0.8; rs324011, rs167769, or rs12368672) associated with a 2.3-2.8-fold increase in odds of relapse of EoE and with a 2.8-4.1-fold increase in odds of 6-14 eos/hpf. For rs324011, the odds ratio for relapse was 2.77 (95% CI, 1.11-6.92; P=.029; and the odds ratio for 6-14 eos/hpf was 3.06 (95% CI, 1.27-7.36; P=.012).Pediatric EoE patients who initially respond to PPI therapy and carry STAT6 variants rs324011, rs167769 or rs12368672 are at increased risk of relapse following 1 year of PPI maintenance therapy.


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