A genome-wide association study of sodium levels and drug metabolism in an epilepsy cohort treated with carbamazepine and oxcarbazepine
File(s)Berghuis_et_al-2019-Epilepsia_Open.pdf (251.07 KB)
Published version
Author(s)
Type
Journal Article
Abstract
Epilepsia 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.
Date Issued
2019-03-01
Date Acceptance
2018-12-06
Citation
Epilepsia Open, 2019, 4 (1), pp.102-109
ISSN
2470-9239
Publisher
Wiley
Start Page
102
End Page
109
Journal / Book Title
Epilepsia Open
Volume
4
Issue
1
Copyright Statement
© 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.
provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Commission of the European Communities
Grant Number
RDA03
RD610
279062
Subjects
EpiPGX Consortium
GWAS
adverse effects
antiepileptic drugs
hyponatremia
Publication Status
Published
Date Publish Online
2018-12-23