A genome-wide association study of sodium levels and drug metabolism in an epilepsy cohort treated with carbamazepine and oxcarbazepine
| Title: | A genome-wide association study of sodium levels and drug metabolism in an epilepsy cohort treated with carbamazepine and oxcarbazepine |
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| 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; Avbersek, A.; Leu, C.; Heggeli, K.; Willis, J.; Speed, D.; Sargsyan, N.; Chinthapalli, K.; Borghei, M.; Coppola, A.; Gambardella, A.; Becker, F.; Rau, S.; Hengsbach, C.; Weber, Y. G.; Delanty, N.; Campbell, E.; Gudmundsson, L. J.; Ingason, A.; Stefánsson, K.; Schneider, R.; Jorgensen, A.; Srivastava, P.; Moller, R.; Nikanorova, M. |
| Source: | Berghuis, B, Stapleton, C, Sonsma, A C M, Hulst, J, de Haan, G J, Lindhout, D, Demurtas, R, 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, McCormack, M, The EpiPGX Consortium, Avbersek, A, Leu, C, Heggeli, K, Willis, J, Speed, D, Sargsyan, N, Chinthapalli, K, Borghei, M, Coppola, A, Gambardella, A, Becker, F, Rau, S, Hengsbach, C, Weber, Y G, Delanty, .... |
| Publication Year: | 2019 |
| Collection: | University of Southern Denmark: Research Output / Syddansk Universitet |
| Subject Terms: | adverse effects; antiepileptic drugs; EpiPGX Consortium; GWAS; hyponatremia |
| Description: | 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. |
| Document Type: | article in journal/newspaper |
| File Description: | application/pdf |
| Language: | English |
| ISSN: | 2470-9239 |
| Relation: | info:eu-repo/semantics/altIdentifier/pissn/2470-9239 |
| DOI: | 10.1002/epi4.12297 |
| Availability: | https://portal.findresearcher.sdu.dk/da/publications/7f28d335-73a4-4971-a352-cd20cff657d5; https://doi.org/10.1002/epi4.12297; https://findresearcher.sdu.dk/ws/files/276248772/Epilepsia_Open_-_2018_-_Berghuis_-_A_genome_wide_association_study_of_sodium_levels_and_drug_metabolism_in_an_epilepsy.pdf |
| Rights: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: | edsbas.6041BA40 |
| Database: | BASE |