Impact of <i>STAT6</i> Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis
Proton pump inhibitors (PPIs) are the first-line drug for eosinophilic esophagitis (EoE), although it is estimated that there is a lack of histological remission in 50% of patients. This research aimed to identify pharmacogenetic biomarkers predictive of PPI effectiveness and to study their associat...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-03-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/25/7/3685 |
| Summary: | Proton pump inhibitors (PPIs) are the first-line drug for eosinophilic esophagitis (EoE), although it is estimated that there is a lack of histological remission in 50% of patients. This research aimed to identify pharmacogenetic biomarkers predictive of PPI effectiveness and to study their association with disease features. Peak eosinophil count (PEC) and the endoscopic reference score (EREFS) were determined before and after an eight-week PPI course in 28 EoE patients. The impact of the signal transducer and activator of transcription 6 (<i>STAT6</i>), <i>CYP2C19</i>, <i>CYP3A4</i>, <i>CYP3A5,</i> and <i>ABCB1</i> genetic variations on baseline PEC and EREFS, their reduction and histological response, and on EoE symptoms and comorbidities was analyzed. PEC reduction was higher in omeprazole-treated patients (92.5%) compared to other PPIs (57.9%, <i>p</i> = 0.003). <i>STAT6</i> rs12368672 (g.18453G>C) G/G genotype showed higher baseline PEC values compared to G/C and C/C genotypes (83.2 vs. 52.9, <i>p</i> = 0.027). EREFS reduction in <i>STAT6</i> rs12368672 G/G and G/C genotypes was higher than in the C/C genotype (36.7% vs. −75.0% <i>p</i> = 0.011). However, significance was lost after Bonferroni correction. Heartburn incidence was higher in <i>STAT6</i> rs167769 (g.27148G>A) G/G patients compared to G/A (54.55% vs. 11.77%, <i>p</i> = 0.030). <i>STAT6</i> rs12368672G>C and rs167769G>A variants might have a relevant impact on EoE status and PPI response. Further research is warranted to clarify the clinical relevance of these variants. |
|---|---|
| ISSN: | 1661-6596 1422-0067 |