A genome-wide association study of sodium levels and drug metabolism in an epilepsy cohort treated with carbamazepine and oxcarbazepine
- Creators
- 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.
- 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.
- Stefansson K.
- Schneider R.
- Balling R.
- Francis B.
- Jorgensen A.
- Morris A.
- Langley S.
- Srivastava P.
- Brodie M.
- Todaro M.
- Petrovski S.
- Hutton J.
- Zimprich F.
- Krenn M.
- Muhle H.
- Martin Klein K.
- Moller R.
- Nikanorova M.
- Weckhuysen S.
- Rener-Primec Z.
- Others:
- 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.
- 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.
- Stefansson, K.
- Schneider, R.
- Balling, R.
- Francis, B.
- Jorgensen, A.
- Morris, A.
- Langley, S.
- Srivastava, P.
- Brodie, M.
- Todaro, M.
- Petrovski, S.
- Hutton, J.
- Zimprich, F.
- Krenn, M.
- Muhle, H.
- Martin Klein, K.
- Moller, R.
- Nikanorova, M.
- Weckhuysen, S.
- Rener-Primec, Z.
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.
Additional details
- URL
- http://hdl.handle.net/11567/1021904
- URN
- urn:oai:iris.unige.it:11567/1021904
- Origin repository
- UNIGE