Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study.

Autor: Wolking S; Department of Neurology & Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.; Department of Neurosciences, CHUM Research Center, University of Montreal, Montreal, H2X 0A9, Canada., Schulz H; Cologne Center for Genomics, University of Cologne, 50931 Cologne, Germany., Nies AT; Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany.; University of Tübingen, 72076 Tübingen, Germany., McCormack M; Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, D02 YN77, Ireland., Schaeffeler E; Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany.; University of Tübingen, 72076 Tübingen, Germany., Auce P; Walton Centre NHS Foundation Trust, Liverpool, L33 4YD, UK., Avbersek A; Department of Clinical & Experimental Epilepsy, UCL Queen Square Institute of Neurology, London & Chalfont Centre for Epilepsy, London, SL9 0RJ, UK., Becker F; Department of Neurology & Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany., Klein KM; Epilepsy Center Frankfurt Rhine-Main, University Hospital Frankfurt, Goethe University Frankfurt, 60590 Frankfurt, Germany., Krenn M; Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria., Møller RS; Danish Epilepsy Centre - Filadelfia, 4293 Dianalund, Denmark.; Department of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark., Nikanorova M; Danish Epilepsy Centre - Filadelfia, 4293 Dianalund, Denmark., Weckhuysen S; Neurogenetics Group, Center for Molecular Neurology, VIB-University of Antwerp, 2650 Edegem, Belgium.; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, 2650 Edegem, Belgium.; Department of Neurology, Antwerp University Hospital, 2650 Edegem, Belgium., Consortium E, Cavalleri GL; Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, D02 YN77, Ireland.; Division of Brain Sciences, Imperial College Faculty of Medicine, London, SW2 2AZ, UK., Delanty N; Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, D02 YN77, Ireland.; Division of Neurology, Beaumont Hospital, Dublin 9, Ireland.; The FutureNeuro Research Centre, Royal College of Surgeons in Ireland, Dublin, D02 YN77, Ireland., Depondt C; Department of Neurology, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium., Johnson MR; Division of Brain Sciences, Imperial College Faculty of Medicine, London, SW2 2AZ, UK., Koeleman BP; Department of Genetics, University Medical Center Utrecht, 3584 Utrecht, The Netherlands., Kunz WS; Institute of Experimental Epileptology & Cognition Research & Department of Epileptology, University of Bonn, 53127 Bonn, Germany., Marson AG; Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, L69 7ZB, UK., Sander JW; Department of Clinical & Experimental Epilepsy, UCL Queen Square Institute of Neurology, London & Chalfont Centre for Epilepsy, London, SL9 0RJ, UK.; Stichting Epilepsie Instellingen Nederland (SEIN), 2103 Heemstede, The Netherlands., Sills GJ; Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, L69 7ZB, UK., Striano P; Pediatric Neurology & Muscular Diseases Unit, IRCCS 'G. Gaslini' Institute, 16147 Genova, Italy.; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal & Child Health, University of Genova, 16147 Genova, Italy., Zara F; Laboratory of Neurogenetics and Neuroscience, IRCCS 'G. Gaslini' Institute, 16147 Genova, Italy., Zimprich F; Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria., Weber YG; Department of Neurology & Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany., Krause R; Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg., Sisodiya S; Department of Clinical & Experimental Epilepsy, UCL Queen Square Institute of Neurology, London & Chalfont Centre for Epilepsy, London, SL9 0RJ, UK., Schwab M; Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany.; Department of Clinical Pharmacology, University Hospital Tübingen, 72076 Tübingen, Germany.; Department of Pharmacy & Biochemistry, University Tübingen, 72076 Tübingen, Germany., Sander T; Cologne Center for Genomics, University of Cologne, 50931 Cologne, Germany., Lerche H; Department of Neurology & Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
Jazyk: angličtina
Zdroj: Pharmacogenomics [Pharmacogenomics] 2020 Apr; Vol. 21 (5), pp. 325-335. Date of Electronic Publication: 2020 Apr 20.
DOI: 10.2217/pgs-2019-0179
Abstrakt: Aim: Pharmacoresistance is a major burden in epilepsy treatment. We aimed to identify genetic biomarkers in response to specific antiepileptic drugs (AEDs) in genetic generalized epilepsies (GGE). Materials & methods: We conducted a genome-wide association study (GWAS) of 3.3 million autosomal SNPs in 893 European subjects with GGE - responsive or nonresponsive to lamotrigine, levetiracetam and valproic acid. Results: Our GWAS of AED response revealed suggestive evidence for association at 29 genomic loci (p <10 -5 ) but no significant association reflecting its limited power. The suggestive associations highlight candidate genes that are implicated in epileptogenesis and neurodevelopment. Conclusion: This first GWAS of AED response in GGE provides a comprehensive reference of SNP associations for hypothesis-driven candidate gene analyses in upcoming pharmacogenetic studies.
Databáze: MEDLINE