A genome‐wide association study of sodium levels and drug metabolism in an epilepsy cohort treated with carbamazepine and oxcarbazepine

Berghuis, B. et al. (2019) A genome‐wide association study of sodium levels and drug metabolism in an epilepsy cohort treated with carbamazepine and oxcarbazepine. Epilepsia Open, 4(1), pp. 102-109. (doi: 10.1002/epi4.12297) (PMID:30868120) (PMCID:PMC6398103)

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Abstract

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 anti‐epileptic drug levels in people with epilepsy attending a tertiary epilepsy centre 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 1,141 subjects. We did not observe any genome‐wide significant associations with sodium level in a linear trend or hyponatraemia as a dichotomous trait. Age, sex, number of co‐medications, 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: While we did not detect a genetic predictor of hyponatraemia or CBZ metabolism in our cohort, our findings suggest the determinants of CBZ metabolism are multifactorial.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Auce, Dr Pauls and Sills, Dr Graeme
Authors: Berghuis, B., Stapleton, C., Sonsma, A. C.M., Hulst, J., de Haan, G.-J., Lindhout, D., Demurtas, R., EpiPGX Consortium, , Krause, R., Depondt, C., Kunz, W. S., Zara, F., Striano, P., Craig, J., Auce, P., Marson, A. G., Stefansson, H., O'Brien, T. J., Johnson, M. R., Sills, G. J., Wolking, S., Lerche, H., Sisodiya, S. M., Sander, J. W., Cavalleri, G. L., Koeleman, B. P.C., and McCormack, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Epilepsia Open
Publisher:Wiley
ISSN:2470-9239
ISSN (Online):2470-9239
Published Online:23 December 2018
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Epilepsia Open 4(1):102-109
Publisher Policy:Reproduced under a Creative Commons License

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