{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:56:05Z","timestamp":1791618965169,"version":"4.3.4"},"reference-count":80,"publisher":"American Society for Clinical Investigation","issue":"8","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U19 AI070235"],"award-info":[{"award-number":["U19 AI070235"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,4,19]]},"abstract":"<jats:p>\n                    Eosinophilic esophagitis (EoE) is an allergic inflammatory esophageal disorder with a complex underlying genetic etiology often associated with other comorbidities. Using whole-exome sequencing (WES) of 63 patients with EoE and 60 unaffected family members and family-based trio analysis, we sought to uncover rare coding variants. WES analysis identified 5 rare, damaging variants in dehydrogenase E1 and transketolase domain\u2013containing 1 (\n                    <jats:italic>DHTKD1<\/jats:italic>\n                    ). Rare variant burden analysis revealed an overabundance of putative, potentially damaging\n                    <jats:italic>DHTKD1<\/jats:italic>\n                    mutations in EoE (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.01). Interestingly, we also identified 7 variants in the\n                    <jats:italic>DHTKD1<\/jats:italic>\n                    homolog oxoglutarate dehydrogenase-like (\n                    <jats:italic>OGDHL<\/jats:italic>\n                    ). Using shRNA-transduced esophageal epithelial cells and\/or patient fibroblasts, we further showed that disruption of normal\n                    <jats:italic>DHTKD1<\/jats:italic>\n                    or\n                    <jats:italic>OGDHL<\/jats:italic>\n                    expression blunts mitochondrial function. Finally, we demonstrated that the loss of\n                    <jats:italic>DHTKD1<\/jats:italic>\n                    expression increased ROS production and induced the expression of viperin, a gene previously shown to be involved in production of Th2 cytokines in T cells. Viperin had increased expression in esophageal biopsies of EoE patients compared with control individuals and was upregulated by IL-13 in esophageal epithelial cells. These data identify a series of rare genetic variants implicating\n                    <jats:italic>DHTKD1<\/jats:italic>\n                    and\n                    <jats:italic>OGDHL<\/jats:italic>\n                    in the genetic etiology of EoE and underscore a potential pathogenic role for mitochondrial dysfunction in EoE.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.99922","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T11:02:49Z","timestamp":1524049369000},"source":"Crossref","is-referenced-by-count":55,"title":["Whole-exome sequencing uncovers oxidoreductases DHTKD1 and OGDHL as linkers between mitochondrial dysfunction and eosinophilic esophagitis"],"prefix":"10.1172","volume":"3","author":[{"given":"Joseph D.","family":"Sherrill","sequence":"first","affiliation":[{"name":"Division of Allergy and Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"KC","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjian","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wen","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Chamberlin","sequence":"additional","affiliation":[{"name":"Clinical Genomics, Ambry Genetics, Aliso Viejo, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily M.","family":"Stucke","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret H.","family":"Collins","sequence":"additional","affiliation":[{"name":"Divisions of Pathology and Laboratory Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3788-6485","authenticated-orcid":true,"given":"J. Pablo","family":"Abonia","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1176-4837","authenticated-orcid":true,"given":"Yanyan","family":"Peng","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip E.","family":"Putnam","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip J.","family":"Dexheimer","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce J.","family":"Aronow","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah C.","family":"Kottyan","sequence":"additional","affiliation":[{"name":"Center for Autoimmune Genomics and Etiology, CCHMC, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth M.","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Center for Autoimmune Genomics and Etiology, CCHMC, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA."},{"name":"US Department of 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