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

Bianca Berghuis, Caragh Stapleton, Anja C.M. Sonsma, Janic Hulst, Gerrit Jan de Haan, Dick Lindhout, Rita Demurtas, the EpiPGX Consortium, Roland Krause, Chantal Depondt, Wolfram S. Kunz, Federico Zara, Pasquale Striano, John Craig, Pauls Auce, Anthony G. Marson, Hreinn Stefansson, Terence J. O'Brien, Michael R. Johnson, Graeme J. SillsStefan Wolking, Holger Lerche, Sanjay M. Sisodiya, Josemir W. Sander, Gianpiero L. Cavalleri, Bobby P.C. Koeleman, Mark McCormack

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)102-109
Number of pages8
JournalEpilepsia Open
Volume4
Issue number1
DOIs
Publication statusPublished - 1 Mar 2019
Externally publishedYes

Keywords

  • adverse effects
  • antiepileptic drugs
  • EpiPGX Consortium
  • GWAS
  • hyponatremia

Cite this