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

Autor: Berghuis B; Stichting Epilepsie Instellingen Nederland (SEIN) Zwolle The Netherlands., Stapleton C; Molecular and Cellular Therapeutics Royal College of Surgeons in Ireland Dublin Ireland., Sonsma ACM; Department of Genetics University Medical Center Utrecht Utrecht The Netherlands., Hulst J; Stichting Epilepsie Instellingen Nederland (SEIN) Zwolle The Netherlands., de Haan GJ; Stichting Epilepsie Instellingen Nederland (SEIN) Zwolle The Netherlands., Lindhout D; Stichting Epilepsie Instellingen Nederland (SEIN) Zwolle The Netherlands.; Department of Genetics University Medical Center Utrecht Utrecht The Netherlands., Demurtas R; Department of Clinical and Experimental Epilepsy Institute of Neurology University College London London UK., Krause R; Luxembourg Centre for Systems Biomedicine University of Luxembourg Esch-sur-Alzette Luxembourg., Depondt C; Laboratory of Experimental Neurology Hôpital Erasme Université Libre de Bruxelles Brussels Belgium., Kunz WS; Institute of Experimental Epileptology and Cognition Research and Department of Epileptology University of Bonn Bonn Germany., Zara F; Laboratory of Neurogenetics and Neuroscience Institute G. Gaslini Genova Italy., Striano P; Pediatric Neurology and Muscular Diseases Unit DINOGMI-Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genova Institute 'G. Gaslini' Genova Italy., Craig J; Department of Neurosciences Belfast Health and Social Care Trust Belfast UK., Auce P; Department of Molecular and Clinical Pharmacology Institute of Translational Medicine University of Liverpool Liverpool UK., Marson AG; Department of Molecular and Clinical Pharmacology Institute of Translational Medicine University of Liverpool Liverpool UK., Stefansson H; deCODE Genetics/Amgen, Inc. Reykjavik Iceland., O'Brien TJ; The Departments of Medicine and Neurology The Melbourne Brain Centre The University of Melbourne The Royal Melbourne Hospital Melbourne Australia., Johnson MR; Division of Brain Sciences Imperial College Faculty of Medicine London UK., Sills GJ; Department of Molecular and Clinical Pharmacology Institute of Translational Medicine University of Liverpool Liverpool UK., Wolking S; Department of Neurology and Epileptology University of Tübingen Hertie Institute for Clinical Brain Research Tübingen Germany., Lerche H; Department of Neurology and Epileptology University of Tübingen Hertie Institute for Clinical Brain Research Tübingen Germany., Sisodiya SM; Department of Clinical and Experimental Epilepsy Institute of Neurology University College London London UK.; Chalfont Centre for Epilepsy Chalfont St. Peter UK., Sander JW; Stichting Epilepsie Instellingen Nederland (SEIN) Zwolle The Netherlands.; Department of Clinical and Experimental Epilepsy Institute of Neurology University College London London UK.; Chalfont Centre for Epilepsy Chalfont St. Peter UK., Cavalleri GL; Molecular and Cellular Therapeutics Royal College of Surgeons in Ireland Dublin Ireland.; The FutureNeuro Research Centre Royal College of Surgeons in Ireland Dublin Ireland., Koeleman BPC; Department of Genetics University Medical Center Utrecht Utrecht The Netherlands., McCormack M; Molecular and Cellular Therapeutics Royal College of Surgeons in Ireland Dublin Ireland.; Department of Genetics University Medical Center Utrecht Utrecht The Netherlands.
Jazyk: angličtina
Zdroj: Epilepsia open [Epilepsia Open] 2019 Jan 17; Vol. 4 (1), pp. 102-109. Date of Electronic Publication: 2019 Jan 17 (Print Publication: 2019).
DOI: 10.1002/epi4.12297
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: