title: Increased CPA6 promoter methylation in focal epilepsy and in febrile seizures.
abstract: Focal epilepsy (FE) is one of the most common forms of adult epilepsy and is usually regarded as a multifactorial disorder. Febrile seizures (FS) often appear during childhood in a subtype of FE patients, i.e. with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). FS are the most common human convulsive event associated with fever. Genetic evidences for FS have suggested a complex mode of inheritance. Until now, to investigate genes at the genomic level, linkage analysis of familial forms and association studies have been performed, but nothing conclusive has been clearly related to FE and FS. As complex disorders, environmental factors might play a crucial role through epigenetic modification of key candidate genes such as CPA6, which encodes Carboxypeptidase A6, an extracellular protein. Therefore, we assessed DNA methylation in promoter of CPA6. In 186 FE patients and 92 FS patients compared to 93 healthy controls and 42 treated controls with antiepileptic drugs (AEDs), we found significant higher levels of methylation for epileptic patients. Methylation status were 3.4% (±3.2%) for FE cases and 4.3% (±3.5%) for FS cases, whereas healthy individuals and treated controls with AEDs showed a level of 0.8% (±2.9%) and 1.5% (±3.9%), respectively (p≤0.001 for all comparisons). These results let growing evidence for DNA methylation involvment in FE and FS.
authors.affiliation: Laboratory of Genetic, Immunology and Human Pathologies, Department of Biology, Faculty of Sciences, Tunis, Tunisia; Neurological Department, Charles Nicolle Hospital, Tunis, Tunisia.
authors.forename: N
authors.initials: N
authors.lastname: Belhedi
authors.affiliation: Department of Psychiatry, University of Geneva, Geneva, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Perroud
authors.affiliation: Department of Biology, National University of Rwanda, Rwanda.
authors.forename: F
authors.initials: F
authors.lastname: Karege
authors.affiliation: Department of Genetic Medicine and Laboratory, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Vessaz
authors.affiliation: Department of Psychiatry, University of Geneva, Geneva, Switzerland; Department of Genetic Medicine and Laboratory, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Malafosse
authors.affiliation: Department of Psychiatry, University of Geneva, Geneva, Switzerland. Electronic address: annick.salzmann@hcuge.ch.
authors.forename: A
authors.initials: A
authors.lastname: Salzmann
mesh_terms: D000328:Adult; D001483:Base Sequence; D043422:Carboxypeptidases A / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D019175:DNA Methylation / Q000235:genetics*; D004828:Epilepsies, Partial / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D003294:Seizures, Febrile / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: C578288:CPA6 protein, human; D043422:Carboxypeptidases A
keywords: CPA6; DNA methylation; Febrile seizures; Focal epilepsy