{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T17:24:35Z","timestamp":1767374675698},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T00:00:00Z","timestamp":1537920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007083","name":"Orionin Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007083","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005744","name":"Lastentautien Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005744","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["Decision number 138566"],"award-info":[{"award-number":["Decision number 138566"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2018,11]]},"abstract":"Summary<\/jats:title>Objective<\/jats:title>Previous studies have suggested that heterozygous variants p.Q1236H and p.E1143G in mitochondrial DNA<\/jats:styled-content> polymerase gamma (POLG<\/jats:styled-content>1<\/jats:italic>) increase the risk for liver injury for patients on valproate (VPA<\/jats:styled-content>) therapy. We assessed the prevalence of these common variants and seven other pathogenic mutations in POLG<\/jats:styled-content>1<\/jats:italic> and determined the occurrence of VPA<\/jats:styled-content>\u2010induced hepatotoxicity (VHT<\/jats:styled-content>) or pancreatic toxicity in a cohort of patients with epilepsy.<\/jats:p><\/jats:sec>Methods<\/jats:title>Patients with epilepsy (N = 367) were retrospectively identified from medical record files and screened for mutations in POLG<\/jats:styled-content>1<\/jats:italic>. Patients who had received VPA<\/jats:styled-content> monotherapy and carried either of the two variants, p.Q1236H or p.E1143G, without other pathogenic mutations in POLG<\/jats:styled-content>1<\/jats:italic> (n = 33, variant group) and patients without these variants (n = 28, nonvariant group) were included in the study. Clinical data on epilepsy, characteristics of VPA<\/jats:styled-content> treatment, risk factors for VHT<\/jats:styled-content>, laboratory data on liver and pancreas functions, and adverse effects were collected.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 122 patients had either the POLG<\/jats:styled-content>1<\/jats:italic> p.Q1236H (n = 99) or p.E1143G (n = 24) variant in the heterozygous or homozygous state. Transient liver dysfunction was identified in three (n = 33, 9.1%) variant group patients and in one (n = 28, 3.6%) nonvariant group patient (P<\/jats:italic> = 0.62). Mild to moderate elevations in liver enzymes were encountered in both groups. Furthermore, two patients on VPA<\/jats:styled-content> polytherapy developed acute pancreatitis, and two pediatric patients with heterozygous p.Q1236H variants and mutations in IQSEC<\/jats:styled-content>2<\/jats:italic> and GLDC<\/jats:styled-content><\/jats:italic>, respectively, had elevated levels of VPA<\/jats:styled-content> metabolites in urine, elevated plasma glycine, and\/or increased acylglycine excretion.<\/jats:p><\/jats:sec>Significance<\/jats:title>POLG<\/jats:styled-content>1<\/jats:italic> p.Q1236H and p.E1143G variants could not be identified as statistically significant risk factors for VHT<\/jats:styled-content> or pancreatic toxicity. We suggest that VPA<\/jats:styled-content> treatment could be suitable for patients who harbor these common variants in the absence of other pathogenic mutations in POLG<\/jats:styled-content>1<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.14568","type":"journal-article","created":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T09:38:46Z","timestamp":1537954726000},"page":"2125-2136","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Variants p.Q1236H and p.E1143G in mitochondrial DNA polymerase gamma POLG<\/scp>1<\/i> are not associated with increased risk for valproate\u2010induced hepatotoxicity or pancreatic toxicity: A retrospective cohort study of patients with epilepsy"],"prefix":"10.1111","volume":"59","author":[{"given":"Johanna","family":"Hynynen","sequence":"first","affiliation":[{"name":"Research Unit for Pediatrics, Pediatric Neurology, Pediatric Surgery, Child Psychiatry, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Otorhinolaryngology and Ophthalmology University of Oulu Oulu Finland"},{"name":"Medical Research Center Oulu University Hospital Oulu Finland"},{"name":"Biocenter Oulu University of Oulu Oulu Finland"},{"name":"Department of Children and Adolescents Division of Pediatric Neurology Oulu University Hospital Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tytti","family":"Pokka","sequence":"additional","affiliation":[{"name":"Research Unit for Pediatrics, Pediatric Neurology, Pediatric Surgery, Child Psychiatry, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Otorhinolaryngology and Ophthalmology University of Oulu Oulu Finland"},{"name":"Department of Children and Adolescents Division of Pediatric Neurology Oulu University Hospital Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonna","family":"Komulainen\u2010Ebrahim","sequence":"additional","affiliation":[{"name":"Research Unit for Pediatrics, Pediatric Neurology, Pediatric Surgery, Child Psychiatry, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Otorhinolaryngology and Ophthalmology University of Oulu Oulu Finland"},{"name":"Medical Research Center Oulu University Hospital Oulu Finland"},{"name":"Biocenter Oulu University of Oulu Oulu Finland"},{"name":"Department of Children and Adolescents Division of Pediatric Neurology Oulu University Hospital Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e4ivi","family":"Myllynen","sequence":"additional","affiliation":[{"name":"Nordlab Oulu Oulu University Hospital Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikko","family":"K\u00e4rpp\u00e4","sequence":"additional","affiliation":[{"name":"Medical Research Center Oulu University Hospital Oulu Finland"},{"name":"Department of Neurology Oulu University Hospital Oulu Finland"},{"name":"Research Unit of Clinical Neuroscience, Neurology University of Oulu Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Pylv\u00e4nen","sequence":"additional","affiliation":[{"name":"Department of Neurology Oulu University Hospital Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reetta","family":"K\u00e4lvi\u00e4inen","sequence":"additional","affiliation":[{"name":"Department of Neurology Kuopio University Hospital Kuopio Finland"},{"name":"Institute of Clinical Medicine School of Medicine Faculty of Health Sciences University of Eastern Finland Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arja","family":"Sokka","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine School of Medicine Faculty of Health Sciences University of Eastern 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