{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T01:29:59Z","timestamp":1774574999581,"version":"3.50.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:00:00Z","timestamp":1686873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100005731","name":"Juntendo University","doi-asserted-by":"publisher","award":["GP21-39"],"award-info":[{"award-number":["GP21-39"]}],"id":[{"id":"10.13039\/501100005731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007786","name":"National Center for Child Health and Development","doi-asserted-by":"publisher","award":["2019A-3"],"award-info":[{"award-number":["2019A-3"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Japanese Ministry of Health, Labour, and Welfare","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>SLCO2A1 encodes a prostaglandin (PG) transporter, and autosomal recessive pathogenic variants of this gene cause chronic enteropathy associated with SLCO2A1. It is unclear whether a heterozygous pathogenic variant of SLCO2A1 has a role in the pathogenesis of other types of inflammatory bowel disease (IBD). In this study, we investigated the possible involvement of a local epigenetic alteration in SLCO2A1 in patients with a heterozygous pathogenic variant.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted whole-exome sequencing of samples from 2 sisters with suspected monogenic IBD. In addition, we performed bisulfite sequencing using DNA extracted from their small and large intestine samples to explore epigenetic alterations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A heterozygous splicing site variant, SLCO2A1:c.940\u2005+\u20051G\u2005&amp;gt;\u2005A, was detected in both patients. To explore the possible involvement of epigenetic alterations, we analyzed protein and messenger RNA expression of SLCO2A1, and observed attenuated SLCO2A1 expression in the inflamed lesions of these patients compared with that in the control individuals. Furthermore, bisulfite sequencing indicated dense methylation in the promoter region of SLCO2A1 only in the inflamed lesions of both patients. The urinary PG metabolite levels in these patients were comparable to those in patients with chronic enteropathy associated with SLCO2A1 and higher than those in the control individuals. We found considerably higher levels of the metabolites in patient 1, who showed more severe symptoms than patient 2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Local DNA methylation attenuated SLCO2A1 expression, which may evoke local inflammation of the mucosa by the unincorporated PG. These findings may improve our understanding of the epigenetic mechanisms underlying IBD development.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izad116","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T16:20:03Z","timestamp":1686932403000},"page":"1920-1928","source":"Crossref","is-referenced-by-count":7,"title":["Attenuated Expression of <i>SLCO2A1<\/i> Caused by DNA Methylation in Pediatric Inflammatory Bowel Disease"],"prefix":"10.1093","volume":"29","author":[{"given":"Natsuki","family":"Ito","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine , Tokyo , Japan"},{"name":"Diagnostics and Therapeutics of Intractable Diseases and Intractable Disease Research Center, Juntendo University Graduate School of Medicine , Tokyo , 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