{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T19:33:54Z","timestamp":1774726434987,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,7,19]],"date-time":"2018-07-19T00:00:00Z","timestamp":1531958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673510"],"award-info":[{"award-number":["81673510"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2018,11]]},"abstract":"Abstract<\/jats:title>This study was aimed at identifying genetic and non\u2010genetic risk factors for valproic acid (VPA<\/jats:styled-content>)\u2010induced hyperammonaemia in Chinese paediatric patients with epilepsy. A total of 210 epileptic patients, treated with VPA<\/jats:styled-content> as monotherapy, were enrolled and classified into hyperammonaemia and control groups according to their blood ammonia level (cut\u2010off value 50\u00a0\u03bcmol\/L). Serum concentrations of VPA<\/jats:styled-content> and its major metabolites were simultaneously determined by ultrahigh\u2010performance liquid chromatography\u2013tandem mass spectrometry. Six single nucleotide polymorphisms in the candidate genes, CYP<\/jats:styled-content>2C9<\/jats:italic>, CYP<\/jats:styled-content>2A6<\/jats:italic>, CYP<\/jats:styled-content>2B6<\/jats:italic> and CPS<\/jats:styled-content>1<\/jats:italic>, were analysed by a matrix\u2010assisted laser desorption ionization\u2010time of flight mass spectrometry method or nested PCR<\/jats:styled-content>. Significant differences in age, aspartate transaminase level and the incidence of liver injury were observed between patients of hyperammonaemia and control groups. Genotype distributions of CYP<\/jats:styled-content>2C9*3<\/jats:italic>, CYP<\/jats:styled-content>2A6*4<\/jats:italic> and CPS<\/jats:styled-content>1<\/jats:italic> 4217C>A allelic variants were also significantly different between the two groups. According to multiple regression analysis, a significant negative correlation was detected between age and the blood ammonia level, while liver injury, the concentration\u2013dose ratio (CDR<\/jats:styled-content>) of VPA<\/jats:styled-content> and 2\u2010propyl\u20104\u2010pentenoic acid (4\u2010ene VPA<\/jats:styled-content>), and the presence of CYP<\/jats:styled-content>2A6*4<\/jats:italic> or CPS<\/jats:styled-content>1<\/jats:italic> 4217C>A showed positive\u00a0correlations\u00a0with the blood ammonia level. In addition, the risk factors for hyperammonaemia identified by logistic regression analysis were as follows: a younger age (odds ratio [OR<\/jats:styled-content>]\u00a0=\u00a00.85; 95% confidence interval [CI<\/jats:styled-content>]\u00a0=\u00a00.76\u20130.96; p\u00a0<\/jats:italic>=\u00a00.007), occurrence of liver injury (OR<\/jats:styled-content>\u00a0=\u00a04.60; 95% CI<\/jats:styled-content>\u00a0=\u00a01.27\u201316.74; p\u00a0<\/jats:italic>=\u00a00.021), higher CDR<\/jats:styled-content> of 4\u2010ene VPA<\/jats:styled-content> (OR<\/jats:styled-content>\u00a0=\u00a01.08; 95% CI<\/jats:styled-content>\u00a0=\u00a01.03\u20131.14; p<\/jats:italic>\u00a0=\u00a00.001), and carrying mutant alleles of CYP<\/jats:styled-content>2C9*3<\/jats:italic> (OR<\/jats:styled-content>\u00a0=\u00a03.42; 95% CI<\/jats:styled-content>\u00a0=\u00a01.15\u201310.19; p<\/jats:italic>\u00a0=\u00a00.028), CYP<\/jats:styled-content>2A6*4<\/jats:italic> (OR<\/jats:styled-content>\u00a0=\u00a03.23; 95% CI<\/jats:styled-content>\u00a0=\u00a01.40\u20137.48; p<\/jats:italic>\u00a0=\u00a00.006) and CPS<\/jats:styled-content>1<\/jats:italic> 4217C>A (OR<\/jats:styled-content>\u00a0=\u00a03.25; 95% CI<\/jats:styled-content>\u00a0=\u00a01.52\u20136.94; p<\/jats:italic>\u00a0=\u00a00.002). Our findings indicated that multiple genetic and non\u2010genetic risk factors that were identified can be used to predict the development of VPA<\/jats:styled-content>\u2010induced hyperammonaemia in Chinese paediatric patients with epilepsy.<\/jats:p>","DOI":"10.1111\/bcpt.13049","type":"journal-article","created":{"date-parts":[[2018,5,23]],"date-time":"2018-05-23T14:56:07Z","timestamp":1527087367000},"page":"628-634","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Risk Factors for Valproic Acid\u2010induced Hyperammonaemia in Chinese Paediatric Patients with Epilepsy"],"prefix":"10.1111","volume":"123","author":[{"given":"Xu","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Pharmacy Shengjing Hospital of China Medical University Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinlin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital) Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ti","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shengjing Hospital of China Medical University Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Limei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shengjing Hospital of China Medical University Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,7,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2013.06.012"},{"key":"e_1_2_8_3_1","first-page":"6242314","article-title":"Valproic acid induced hyperammonemia in a long time treated patient","volume":"2016","author":"Aiyer 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