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



Berghuis, Bianca, Stapleton, Caragh, Sonsma, Anja CM, Hulst, Janic, de Haan, Gerrit-Jan, Lindhout, Dick, Demurtas, Rita, EpiPGX Consortium, , Krause, Roland, Depondt, Chantal
et al (show 17 more authors) (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). 102 - 109.

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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 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.

Item Type: Article
Uncontrolled Keywords: EpiPGX Consortium
Depositing User: Symplectic Admin
Date Deposited: 10 May 2019 09:01
Last Modified: 06 Nov 2019 21:10
DOI: 10.1002/epi4.12297
Open Access URL: https://doi.org/10.1002/epi4.12297
URI: http://livrepository.liverpool.ac.uk/id/eprint/3040581
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