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No evidence for a BRD 2 promoter hypermethylation in blood leukocytes of Europeans with juvenile myoclonic epilepsy
Author(s) -
Schulz Herbert,
Ruppert AnnKathrin,
Zara Federico,
Madia Francesca,
Iacomino Michele,
S. Vari Maria,
Balagura Ganna,
Minetti Carlo,
Striano Pasquale,
Bianchi Amedeo,
Marini Carla,
Guerrini Renzo,
Weber Yvonne G.,
Becker Felicitas,
Lerche Holger,
Kapser Claudia,
Schankin Christoph J.,
Kunz Wolfram S.,
Møller Rikke S.,
Oliver Karen L.,
Bellows Susannah T.,
Mullen Saul A.,
Berkovic Samuel F.,
Scheffer Ingrid E.,
Caglayan Hande,
Ozbek Ugur,
Hoffmann Per,
Schramm Sara,
Tsortouktzidis Despina,
Becker Albert J.,
Sander Thomas
Publication year - 2019
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.14657
Subject(s) - juvenile myoclonic epilepsy , methylation , epigenetics , dna methylation , cpg site , genetics , single nucleotide polymorphism , biology , genetic association , snp , allele , promoter , epilepsy , gene , genotype , gene expression , neuroscience
Summary Juvenile myoclonic epilepsy ( JME ) is a common syndrome of genetic generalized epilepsies ( GGE s). Linkage and association studies suggest that the gene encoding the bromodomain‐containing protein 2 ( BRD 2 ) may increase risk of JME . The present methylation and association study followed up a recent report highlighting that the BRD 2 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 BRD 2 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 (me QTL , P = 0.55). Our results do not support the previous observation that a high DNA methylation level of the BRD 2 promoter CpG76 island is a prevalent epigenetic motif associated with JME in Caucasians.