A genome‐wide association study of sodium levels and drug metabolism in an epilepsy cohort treated with carbamazepine and oxcarbazepine. Issue 1 (17th January 2019)

• Record Type: Journal Article
• Authors: Berghuis, Bianca; Stapleton, Caragh; Sonsma, Anja C. M.; Hulst, Janic; de Haan, Gerrit‐Jan; Lindhout, Dick; Demurtas, Rita; Krause, Roland; Depondt, Chantal; Kunz, Wolfram S.; Zara, Federico; Striano, Pasquale; Craig, John; Auce, Pauls; Marson, Anthony G.; Stefansson, Hreinn; O'Brien, Terence J.; Johnson, Michael R.; Sills, Graeme J.; Wolking, Stefan; Lerche, Holger; Sisodiya, Sanjay M.; Sander, Josemir W.; Cavalleri, Gianpiero L.; Koeleman, Bobby P. C.; McCormack, Mark
• Other Names: Avbersek Andreja investigator.; Leu Costin investigator.; Heggeli Kristin investigator.; Willis Joseph investigator.; Speed Douglas investigator.; Sargsyan Narek investigator.; Chinthapalli Krishna investigator.; Borghei Mojgansadat investigator.; Coppola Antonietta investigator.; Gambardella Antonio investigator.; Becker Felicitas investigator.; Rau Sarah investigator.; Hengsbach Christian investigator.; Weber Yvonne G. investigator.; Delanty Norman investigator.; Campbell Ellen investigator.; Gudmundsson Lárus J. investigator.; Ingason Andres investigator.; Stefánsson Kári investigator.; Schneider Reinhard investigator.; Balling Rudi investigator.; Francis Ben investigator.; Jorgensen Andrea investigator.; Morris Andrew investigator.; Langley Sarah investigator.; Srivastava Prashant investigator.; Brodie Martin investigator.; Todaro Marian investigator.; Petrovski Slave investigator.; Hutton Jane investigator.; Zimprich Fritz investigator.; Krenn Martin investigator.; Muhle Hiltrud investigator.; Martin Klein Karl investigator.; Moller Rikke investigator.; Nikanorova Marina investigator.; Weckhuysen Sarah investigator.; Rener‐Primec Zvonka investigator.;
• Is Part Of: Epilepsia open. Volume 4:Issue 1(2019)
• Page Start: 102
• Page End: 109
• Publication Date: 2019-01-17
• Subjects: adverse effects -- antiepileptic drugs -- EpiPGX Consortium -- GWAS -- hyponatremia; Epilepsy -- Periodicals; Epilepsy -- Research -- Periodicals; Epilepsy; Periodicals; Fulltext; Internet Resources; Periodicals; 616.853005
• DOI: 10.1002/epi4.12297
• Languages: English
• ISSNs: 2470-9239

Abstract

Summary: 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.