{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T20:47:58Z","timestamp":1778186878579,"version":"3.51.4"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T00:00:00Z","timestamp":1547683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001596","name":"Irish Research Council for Science, Engineering and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001596","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["751761"],"award-info":[{"award-number":["751761"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["13\/CDA\/2223"],"award-info":[{"award-number":["13\/CDA\/2223"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To ascertain the clinical and genetic factors contributing to carbamazepine\u2010 and oxcarbazepine\u2010induced hyponatremia (<jats:styled-content style=\"fixed-case\">COIH<\/jats:styled-content>), and to carbamazepine (<jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content>) metabolism, in a retrospectively collected, cross\u2010sectional cohort of people with epilepsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected data on serum sodium levels and antiepileptic drug levels in people with epilepsy attending a tertiary epilepsy center while on treatment with <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">OXC<\/jats:styled-content>. We defined hyponatremia as Na+ \u2264134 mEq\/L. We estimated the <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content> metabolic ratio defined as the log transformation of the ratio of metabolite <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content>\u2010diol to unchanged drug precursor substrate as measured in serum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Clinical and genetic data relating to carbamazepine and oxcarbazepine trials were collected in 1141 patients. We did not observe any genome\u2010wide significant associations with sodium level in a linear trend or hyponatremia as a dichotomous trait. Age, sex, number of comedications, phenytoin use, phenobarbital use, and sodium valproate use were significant predictors of <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content> metabolic ratio. No genome\u2010wide significant associations with <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content> metabolic ratio were found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Although we did not detect a genetic predictor of hyponatremia or <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content> metabolism in our cohort, our findings suggest that the determinants of <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content> metabolism are multifactorial.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12297","type":"journal-article","created":{"date-parts":[[2018,12,23]],"date-time":"2018-12-23T09:34:00Z","timestamp":1545557640000},"page":"102-109","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A genome\u2010wide association study of sodium levels and drug metabolism in an epilepsy cohort treated with carbamazepine and oxcarbazepine"],"prefix":"10.1002","volume":"4","author":[{"given":"Bianca","family":"Berghuis","sequence":"first","affiliation":[{"name":"Stichting Epilepsie Instellingen Nederland (SEIN)  Zwolle The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caragh","family":"Stapleton","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Therapeutics Royal College of Surgeons in Ireland  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja C. M.","family":"Sonsma","sequence":"additional","affiliation":[{"name":"Department of Genetics University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janic","family":"Hulst","sequence":"additional","affiliation":[{"name":"Stichting Epilepsie Instellingen Nederland (SEIN)  Zwolle The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerrit\u2010Jan","family":"de Haan","sequence":"additional","affiliation":[{"name":"Stichting Epilepsie Instellingen Nederland (SEIN)  Zwolle The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9580-624X","authenticated-orcid":false,"given":"Dick","family":"Lindhout","sequence":"additional","affiliation":[{"name":"Stichting Epilepsie Instellingen Nederland (SEIN)  Zwolle The Netherlands"},{"name":"Department of Genetics University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Demurtas","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy Institute of Neurology University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"The EpiPGX Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Krause","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine University of Luxembourg  Esch\u2010sur\u2010Alzette Luxembourg"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantal","family":"Depondt","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neurology H\u00f4pital Erasme Universit\u00e9 Libre de Bruxelles  Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfram S.","family":"Kunz","sequence":"additional","affiliation":[{"name":"Institute of Experimental Epileptology and Cognition Research and Department of Epileptology University of Bonn  Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Zara","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics and Neuroscience Institute G. Gaslini  Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6065-1476","authenticated-orcid":false,"given":"Pasquale","family":"Striano","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Muscular Diseases Unit DINOGMI\u2010Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genova Institute \u201cG. Gaslini\u201d  Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Craig","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Belfast Health and Social Care Trust  Belfast UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pauls","family":"Auce","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology Institute of Translational Medicine University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony G.","family":"Marson","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology Institute of Translational Medicine University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hreinn","family":"Stefansson","sequence":"additional","affiliation":[{"name":"deCODE Genetics\/Amgen, Inc.  Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terence J.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"The Departments of Medicine and Neurology The Melbourne Brain Centre The University of Melbourne The Royal Melbourne Hospital  Melbourne Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael R.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Division of Brain Sciences Imperial College Faculty of Medicine  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graeme J.","family":"Sills","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology Institute of Translational Medicine University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Wolking","sequence":"additional","affiliation":[{"name":"Department of Neurology and Epileptology University of T\u00fcbingen Hertie Institute for Clinical Brain Research  T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Lerche","sequence":"additional","affiliation":[{"name":"Department of Neurology and Epileptology University of T\u00fcbingen Hertie Institute for Clinical Brain Research  T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay M.","family":"Sisodiya","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy Institute of Neurology University College London  London UK"},{"name":"Chalfont Centre for Epilepsy  Chalfont St. Peter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6041-9661","authenticated-orcid":false,"given":"Josemir W.","family":"Sander","sequence":"additional","affiliation":[{"name":"Stichting Epilepsie Instellingen Nederland (SEIN)  Zwolle The Netherlands"},{"name":"Department of Clinical and Experimental Epilepsy Institute of Neurology University College London  London UK"},{"name":"Chalfont Centre for Epilepsy  Chalfont St. Peter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9802-0506","authenticated-orcid":false,"given":"Gianpiero L.","family":"Cavalleri","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Therapeutics Royal College of Surgeons in Ireland  Dublin Ireland"},{"name":"The FutureNeuro Research Centre Royal College of Surgeons in Ireland  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bobby P. C.","family":"Koeleman","sequence":"additional","affiliation":[{"name":"Department of Genetics University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8213-6141","authenticated-orcid":false,"given":"Mark","family":"McCormack","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Therapeutics Royal College of Surgeons in Ireland  Dublin Ireland"},{"name":"Department of Genetics University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,1,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/428486a"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1013297"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq537"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000001422"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13069"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfq324"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00157.2009"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13777"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13871"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004853"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.11.011"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01261-5"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2156-9-36"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3109\/01677063.2016.1155571"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-004-0878-1"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0142408"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(92)90674-8"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-198109000-00008"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1985.tb05657.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2018.1486707"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199612000-00006"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2013.07.016"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2018.03.023"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2017.1248399"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfq317"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13730-017-0295-9"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI89812"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016080892"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fepi4.12297","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.12297","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T02:45:21Z","timestamp":1694659521000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.12297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,17]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1002\/epi4.12297"],"URL":"https:\/\/doi.org\/10.1002\/epi4.12297","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"value":"2470-9239","type":"print"},{"value":"2470-9239","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,17]]},"assertion":[{"value":"2018-08-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}