STAT6 Variants Associate With Relapse of Eosinophilic Esophagitis in Patients Receiving Long-term Proton Pump Inhibitor Therapy. Mougey, E. B., Nguyen, V., Gutiérrez-Junquera, C., Fernández-Fernández, S., Cilleruelo, M. L., Rayo, A., Borrell, B., Román, E., González-Lois, C., Chao, M., Al-Atrash, H., & Franciosi, J. P. Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association, 19(10):2046–2053.e2, October, 2021. doi abstract bibtex BACKGROUND & AIMS: Based on histologic features, variants in STAT6 are associated with a poor initial response to proton pump inhibitor (PPI) therapy in pediatric patients with eosinophilic esophagitis (EoE). We investigated whether these genetic variants are associated with a poor long-term response in children with EoE who initially responded to PPI therapy. METHODS: We performed a prospective longitudinal cohort study of children ages 2 to 16 years who met the diagnostic criteria for EoE (≥15 eosinophils/high-power field [eos/hpf]), responded to 8 weeks of treatment with 2 mg/kg/d PPI (\textless15 eos/hpf), and whose dose then was reduced to 1 mg/kg/d PPI (maintenance therapy) for 1 year, at which point biopsy specimens were collected by endoscopy. Genomic DNA was isolated from formalin-fixed paraffin-embedded biopsy tissue and was genotyped for variants of STAT6. Remission of inflammation was assessed at eos/hpf thresholds of \textless15 and ≤5. RESULTS: Among 73 patients who received 1 mg/kg/d PPI maintenance therapy for 1 year, 13 patients (18%) had 6 to 14 eos/hpf, 36 patients (49%) had 5 or fewer eos/hpf, and 24 patients (33%) relapsed to EoE (≥15 eos/hpf). Carriage of any of 3 STAT6 variants in linkage disequilibrium (r2 ≥0.8; rs324011, rs167769, or rs12368672) was associated with a 2.3- to 2.8-fold increase in the odds of EoE relapse, and with a 2.8- to 4.1-fold increase in the odds of having 6 to 14 eos/hpf. For rs324011, the odds ratio [95% CI] for relapse was 2.77 [1.11, 6.92]; P = .029, and the odds ratio [95% CI] for having 6 to 14 eos/hpf was 3.06 [1.27, 7.36]; P = .012. CONCLUSIONS: Pediatric EoE patients who initially respond to PPI therapy and carry STAT6 variants rs324011, rs167769, or rs12368672 are at increased risk of relapse after 1 year of PPI maintenance therapy.
@article{mougey_stat6_2021,
title = {{STAT6} {Variants} {Associate} {With} {Relapse} of {Eosinophilic} {Esophagitis} in {Patients} {Receiving} {Long}-term {Proton} {Pump} {Inhibitor} {Therapy}},
volume = {19},
issn = {1542-7714},
doi = {10.1016/j.cgh.2020.08.020},
abstract = {BACKGROUND \& AIMS: Based on histologic features, variants in STAT6 are associated with a poor initial response to proton pump inhibitor (PPI) therapy in pediatric patients with eosinophilic esophagitis (EoE). We investigated whether these genetic variants are associated with a poor long-term response in children with EoE who initially responded to PPI therapy.
METHODS: We performed a prospective longitudinal cohort study of children ages 2 to 16 years who met the diagnostic criteria for EoE (≥15 eosinophils/high-power field [eos/hpf]), responded to 8 weeks of treatment with 2 mg/kg/d PPI ({\textless}15 eos/hpf), and whose dose then was reduced to 1 mg/kg/d PPI (maintenance therapy) for 1 year, at which point biopsy specimens were collected by endoscopy. Genomic DNA was isolated from formalin-fixed paraffin-embedded biopsy tissue and was genotyped for variants of STAT6. Remission of inflammation was assessed at eos/hpf thresholds of {\textless}15 and ≤5.
RESULTS: Among 73 patients who received 1 mg/kg/d PPI maintenance therapy for 1 year, 13 patients (18\%) had 6 to 14 eos/hpf, 36 patients (49\%) had 5 or fewer eos/hpf, and 24 patients (33\%) relapsed to EoE (≥15 eos/hpf). Carriage of any of 3 STAT6 variants in linkage disequilibrium (r2 ≥0.8; rs324011, rs167769, or rs12368672) was associated with a 2.3- to 2.8-fold increase in the odds of EoE relapse, and with a 2.8- to 4.1-fold increase in the odds of having 6 to 14 eos/hpf. For rs324011, the odds ratio [95\% CI] for relapse was 2.77 [1.11, 6.92]; P = .029, and the odds ratio [95\% CI] for having 6 to 14 eos/hpf was 3.06 [1.27, 7.36]; P = .012.
CONCLUSIONS: Pediatric EoE patients who initially respond to PPI therapy and carry STAT6 variants rs324011, rs167769, or rs12368672 are at increased risk of relapse after 1 year of PPI maintenance therapy.},
language = {eng},
number = {10},
journal = {Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association},
author = {Mougey, Edward B. and Nguyen, Vivian and Gutiérrez-Junquera, Carolina and Fernández-Fernández, Sonia and Cilleruelo, Maria Luz and Rayo, Ana and Borrell, Belén and Román, Enriqueta and González-Lois, Carmen and Chao, Montserrat and Al-Atrash, Hadeel and Franciosi, James P.},
month = oct,
year = {2021},
keywords = {Adolescent, Biomarker, Child, Child, Preschool, Eosinophilic Esophagitis, Esophagus, Humans, Immune Response, Longitudinal Studies, Prospective Studies, Proton Pump Inhibitors, Recurrence, Response to Treatment, STAT6 Transcription Factor},
pages = {2046--2053.e2},
}
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{"_id":"rHgZB5zmRNesp4Nwp","bibbaseid":"mougey-nguyen-gutirrezjunquera-fernndezfernndez-cilleruelo-rayo-borrell-romn-etal-stat6variantsassociatewithrelapseofeosinophilicesophagitisinpatientsreceivinglongtermprotonpumpinhibitortherapy-2021","author_short":["Mougey, E. B.","Nguyen, V.","Gutiérrez-Junquera, C.","Fernández-Fernández, S.","Cilleruelo, M. L.","Rayo, A.","Borrell, B.","Román, E.","González-Lois, C.","Chao, M.","Al-Atrash, H.","Franciosi, J. P."],"bibdata":{"bibtype":"article","type":"article","title":"STAT6 Variants Associate With Relapse of Eosinophilic Esophagitis in Patients Receiving Long-term Proton Pump Inhibitor Therapy","volume":"19","issn":"1542-7714","doi":"10.1016/j.cgh.2020.08.020","abstract":"BACKGROUND & AIMS: Based on histologic features, variants in STAT6 are associated with a poor initial response to proton pump inhibitor (PPI) therapy in pediatric patients with eosinophilic esophagitis (EoE). We investigated whether these genetic variants are associated with a poor long-term response in children with EoE who initially responded to PPI therapy. METHODS: We performed a prospective longitudinal cohort study of children ages 2 to 16 years who met the diagnostic criteria for EoE (≥15 eosinophils/high-power field [eos/hpf]), responded to 8 weeks of treatment with 2 mg/kg/d PPI (\\textless15 eos/hpf), and whose dose then was reduced to 1 mg/kg/d PPI (maintenance therapy) for 1 year, at which point biopsy specimens were collected by endoscopy. Genomic DNA was isolated from formalin-fixed paraffin-embedded biopsy tissue and was genotyped for variants of STAT6. Remission of inflammation was assessed at eos/hpf thresholds of \\textless15 and ≤5. RESULTS: Among 73 patients who received 1 mg/kg/d PPI maintenance therapy for 1 year, 13 patients (18%) had 6 to 14 eos/hpf, 36 patients (49%) had 5 or fewer eos/hpf, and 24 patients (33%) relapsed to EoE (≥15 eos/hpf). Carriage of any of 3 STAT6 variants in linkage disequilibrium (r2 ≥0.8; rs324011, rs167769, or rs12368672) was associated with a 2.3- to 2.8-fold increase in the odds of EoE relapse, and with a 2.8- to 4.1-fold increase in the odds of having 6 to 14 eos/hpf. For rs324011, the odds ratio [95% CI] for relapse was 2.77 [1.11, 6.92]; P = .029, and the odds ratio [95% CI] for having 6 to 14 eos/hpf was 3.06 [1.27, 7.36]; P = .012. CONCLUSIONS: Pediatric EoE patients who initially respond to PPI therapy and carry STAT6 variants rs324011, rs167769, or rs12368672 are at increased risk of relapse after 1 year of PPI maintenance therapy.","language":"eng","number":"10","journal":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","author":[{"propositions":[],"lastnames":["Mougey"],"firstnames":["Edward","B."],"suffixes":[]},{"propositions":[],"lastnames":["Nguyen"],"firstnames":["Vivian"],"suffixes":[]},{"propositions":[],"lastnames":["Gutiérrez-Junquera"],"firstnames":["Carolina"],"suffixes":[]},{"propositions":[],"lastnames":["Fernández-Fernández"],"firstnames":["Sonia"],"suffixes":[]},{"propositions":[],"lastnames":["Cilleruelo"],"firstnames":["Maria","Luz"],"suffixes":[]},{"propositions":[],"lastnames":["Rayo"],"firstnames":["Ana"],"suffixes":[]},{"propositions":[],"lastnames":["Borrell"],"firstnames":["Belén"],"suffixes":[]},{"propositions":[],"lastnames":["Román"],"firstnames":["Enriqueta"],"suffixes":[]},{"propositions":[],"lastnames":["González-Lois"],"firstnames":["Carmen"],"suffixes":[]},{"propositions":[],"lastnames":["Chao"],"firstnames":["Montserrat"],"suffixes":[]},{"propositions":[],"lastnames":["Al-Atrash"],"firstnames":["Hadeel"],"suffixes":[]},{"propositions":[],"lastnames":["Franciosi"],"firstnames":["James","P."],"suffixes":[]}],"month":"October","year":"2021","keywords":"Adolescent, Biomarker, Child, Child, Preschool, Eosinophilic Esophagitis, Esophagus, Humans, Immune Response, Longitudinal Studies, Prospective Studies, Proton Pump Inhibitors, Recurrence, Response to Treatment, STAT6 Transcription Factor","pages":"2046–2053.e2","bibtex":"@article{mougey_stat6_2021,\n\ttitle = {{STAT6} {Variants} {Associate} {With} {Relapse} of {Eosinophilic} {Esophagitis} in {Patients} {Receiving} {Long}-term {Proton} {Pump} {Inhibitor} {Therapy}},\n\tvolume = {19},\n\tissn = {1542-7714},\n\tdoi = {10.1016/j.cgh.2020.08.020},\n\tabstract = {BACKGROUND \\& AIMS: Based on histologic features, variants in STAT6 are associated with a poor initial response to proton pump inhibitor (PPI) therapy in pediatric patients with eosinophilic esophagitis (EoE). We investigated whether these genetic variants are associated with a poor long-term response in children with EoE who initially responded to PPI therapy.\nMETHODS: We performed a prospective longitudinal cohort study of children ages 2 to 16 years who met the diagnostic criteria for EoE (≥15 eosinophils/high-power field [eos/hpf]), responded to 8 weeks of treatment with 2 mg/kg/d PPI ({\\textless}15 eos/hpf), and whose dose then was reduced to 1 mg/kg/d PPI (maintenance therapy) for 1 year, at which point biopsy specimens were collected by endoscopy. Genomic DNA was isolated from formalin-fixed paraffin-embedded biopsy tissue and was genotyped for variants of STAT6. Remission of inflammation was assessed at eos/hpf thresholds of {\\textless}15 and ≤5.\nRESULTS: Among 73 patients who received 1 mg/kg/d PPI maintenance therapy for 1 year, 13 patients (18\\%) had 6 to 14 eos/hpf, 36 patients (49\\%) had 5 or fewer eos/hpf, and 24 patients (33\\%) relapsed to EoE (≥15 eos/hpf). Carriage of any of 3 STAT6 variants in linkage disequilibrium (r2 ≥0.8; rs324011, rs167769, or rs12368672) was associated with a 2.3- to 2.8-fold increase in the odds of EoE relapse, and with a 2.8- to 4.1-fold increase in the odds of having 6 to 14 eos/hpf. For rs324011, the odds ratio [95\\% CI] for relapse was 2.77 [1.11, 6.92]; P = .029, and the odds ratio [95\\% CI] for having 6 to 14 eos/hpf was 3.06 [1.27, 7.36]; P = .012.\nCONCLUSIONS: Pediatric EoE patients who initially respond to PPI therapy and carry STAT6 variants rs324011, rs167769, or rs12368672 are at increased risk of relapse after 1 year of PPI maintenance therapy.},\n\tlanguage = {eng},\n\tnumber = {10},\n\tjournal = {Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association},\n\tauthor = {Mougey, Edward B. and Nguyen, Vivian and Gutiérrez-Junquera, Carolina and Fernández-Fernández, Sonia and Cilleruelo, Maria Luz and Rayo, Ana and Borrell, Belén and Román, Enriqueta and González-Lois, Carmen and Chao, Montserrat and Al-Atrash, Hadeel and Franciosi, James P.},\n\tmonth = oct,\n\tyear = {2021},\n\tkeywords = {Adolescent, Biomarker, Child, Child, Preschool, Eosinophilic Esophagitis, Esophagus, Humans, Immune Response, Longitudinal Studies, Prospective Studies, Proton Pump Inhibitors, Recurrence, Response to Treatment, STAT6 Transcription Factor},\n\tpages = {2046--2053.e2},\n}\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n","author_short":["Mougey, E. 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P."],"key":"mougey_stat6_2021","id":"mougey_stat6_2021","bibbaseid":"mougey-nguyen-gutirrezjunquera-fernndezfernndez-cilleruelo-rayo-borrell-romn-etal-stat6variantsassociatewithrelapseofeosinophilicesophagitisinpatientsreceivinglongtermprotonpumpinhibitortherapy-2021","role":"author","urls":{},"keyword":["Adolescent","Biomarker","Child","Child","Preschool","Eosinophilic Esophagitis","Esophagus","Humans","Immune Response","Longitudinal Studies","Prospective Studies","Proton Pump Inhibitors","Recurrence","Response to Treatment","STAT6 Transcription Factor"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://bibbase.org/zotero-group/Leromela/5826776","dataSources":["tJu2LQsng3WaoKpcL","epXRk2zQpWZQCqqGz"],"keywords":["adolescent","biomarker","child","child","preschool","eosinophilic esophagitis","esophagus","humans","immune response","longitudinal studies","prospective studies","proton pump inhibitors","recurrence","response to treatment","stat6 transcription factor"],"search_terms":["stat6","variants","associate","relapse","eosinophilic","esophagitis","patients","receiving","long","term","proton","pump","inhibitor","therapy","mougey","nguyen","gutiérrez-junquera","fernández-fernández","cilleruelo","rayo","borrell","román","gonzález-lois","chao","al-atrash","franciosi"],"title":"STAT6 Variants Associate With Relapse of Eosinophilic Esophagitis in Patients Receiving Long-term Proton Pump Inhibitor Therapy","year":2021}