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Epilepsia. 2019 May;60(5):e31-e36. doi: 10.1111/epi.14657. Epub 2019 Feb 4.

No evidence for a BRD2 promoter hypermethylation in blood leukocytes of Europeans with juvenile myoclonic epilepsy.

Author information

1
Cologne Center for Genomics, University of Cologne, Cologne, Germany.
2
Laboratory of Neurogenetics and Neuroscience, G. Gaslini Institute, Genoa, Italy.
3
Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa, G. Gaslini Institute, Genoa, Italy.
4
Division of Neurology, Hospital San Donato Arezzo, Arezzo, Italy.
5
Pediatric Neurology and Neurogenetics Unit and Laboratories, A. Meyer Children's Hospital, University of Florence, Florence, Italy.
6
Department of Neurology and Epileptology, Hertie Institute of Clinical Brain Research, University of Tübingen, Tübingen, Germany.
7
Department of Neurology, University of Ulm, Ulm, Germany.
8
Department of Neurology, Großhadern Hospital, University of Munich, Munich, Germany.
9
Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
10
Department of Epileptology, Institute of Experimental Epileptology and Cognition Research, University of Bonn Medical Center, Bonn, Germany.
11
Danish Epilepsy Center, Dianalund, Denmark.
12
Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark.
13
Epilepsy Research Centre, Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
14
Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
15
Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia.
16
Department of Molecular Biology and Genetics, Boğaziçi University, Istanbul, Turkey.
17
Izmir Biomedicine and Genome Center, Izmir, Turkey.
18
Department of Medical Genetics, Faculty of Medicine, Acibadem University, Istanbul, Turkey.
19
Department of Genomics, Life and Brain Center, Institute of Human Genetics, University of Bonn, Bonn, Germany.
20
Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
21
Institute of Medical Genetics and Pathology, University Hospital of Basel, Basel, Switzerland.
22
Institute of Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany.
23
Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany.

Abstract

Juvenile myoclonic epilepsy (JME) is a common syndrome of genetic generalized epilepsies (GGEs). Linkage and association studies suggest that the gene encoding the bromodomain-containing protein 2 (BRD2) may increase risk of JME. The present methylation and association study followed up a recent report highlighting that the BRD2 promoter CpG island (CpG76) is differentially hypermethylated in lymphoblastoid cells from Caucasian patients with JME compared to patients with other GGE subtypes and unaffected relatives. In contrast, we found a uniform low average percentage of methylation (<4.5%) for 13 CpG76-CpGs in whole blood cells from 782 unrelated European Caucasians, including 116 JME patients, 196 patients with genetic absence epilepsies, and 470 control subjects. We also failed to confirm an allelic association of the BRD2 promoter single nucleotide polymorphism (SNP) rs3918149 with JME (Armitage trend test, P = 0.98), and we did not detect a substantial impact of SNP rs3918149 on CpG76 methylation in either 116 JME patients (methylation quantitative trait loci [meQTL], P = 0.29) or 470 German control subjects (meQTL, P = 0.55). Our results do not support the previous observation that a high DNA methylation level of the BRD2 promoter CpG76 island is a prevalent epigenetic motif associated with JME in Caucasians.

KEYWORDS:

BRD2 ; DNA methylation; association analysis; genetic generalized epilepsy; juvenile myoclonic epilepsy

PMID:
30719712
DOI:
10.1111/epi.14657

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