Berghuis, BBBerghuisStapleton, CCStapletonSonsma, ACMACMSonsmaHulst, JJHulstde Haan, GJGJde HaanLindhout, DDLindhoutDemurtas, RRDemurtasKrause, RRKrauseDepondt, CCDepondtKunz, WSWSKunzZara, FFZaraStriano, PPStrianoCraig, JJCraigAuce, PPAuceMarson, AGAGMarsonStefansson, HHStefanssonO'Brien, TJTJO'BrienJohnson, MRMRJohnsonSills, GJGJSillsWolking, SSWolkingLerche, HHLercheSisodiya, SMSMSisodiyaSander, JWJWSanderCavalleri, GLGLCavalleriKoeleman, BPCBPCKoelemanMcCormack, MMMcCormack2019-05-072019-05-072019-03-01Epilepsia Open, 2019, 4 (1), pp.102-1092470-9239http://hdl.handle.net/10044/1/69361Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy. Objective: To ascertain the clinical and genetic factors contributing to carbamazepine- and oxcarbazepine-induced hyponatremia (COIH), and to carbamazepine (CBZ) metabolism, in a retrospectively collected, cross-sectional cohort of people with epilepsy. Methods: We collected data on serum sodium levels and antiepileptic drug levels in people with epilepsy attending a tertiary epilepsy center while on treatment with CBZ or OXC. We defined hyponatremia as Na+ ≤134 mEq/L. We estimated the CBZ metabolic ratio defined as the log transformation of the ratio of metabolite CBZ-diol to unchanged drug precursor substrate as measured in serum. Results: Clinical and genetic data relating to carbamazepine and oxcarbazepine trials were collected in 1141 patients. We did not observe any genome-wide 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 CBZ metabolic ratio. No genome-wide significant associations with CBZ metabolic ratio were found. Significance: Although we did not detect a genetic predictor of hyponatremia or CBZ metabolism in our cohort, our findings suggest that the determinants of CBZ metabolism are multifactorial.© 2019 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.EpiPGX ConsortiumGWASadverse effectsantiepileptic drugshyponatremiaJournal Articlehttps://www.dx.doi.org/10.1002/epi4.12297RDA03RD6102790622470-9239