title: BDNF promoter I methylation correlates between post-mortem human peripheral and brain tissues.
abstract: Several psychiatric disorders have been associated with CpG methylation changes in CG rich promoters of the brain-derived neurotrophic factor (BDNF) mainly by extracting DNA from peripheral blood cells. Whether changes in peripheral DNA methylation can be used as a proxy for brain-specific alterations remains an open question. In this study we aimed to compare DNA methylation levels in BDNF promoter regions in human blood cells, muscle and brain regions using bisulfite-pyrosequencing. We found a significant correlation between the levels of BDNF promoter I methylation measured in quadriceps and vPFC tissues extracted from the same individuals (n = 98, Pearson, r = 0.48, p = 4.5 × 10(-7)). In the hippocampus, BDNF promoter I and IV methylation levels were strongly correlated (Pearson, n = 37, r = 0.74, p = 1.4 × 10(-7)). We found evidence for sex-dependent effect on BDNF promoter methylation levels in the various tissues and blood samples. Taken together, these data indicate a strong intra-individual correlation between peripheral and brain tissue. They also suggest that sex determines methylation patterns in BDNF promoter region across different types of tissue, including muscle, brain, and blood.
authors.affiliation: Department of Psychiatry, University of Geneva, Switzerland; Department of Basic Neurosciences, University of Geneva Medical School, Geneva, Switzerland. Electronic address: ludwig.stenz@unige.ch.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Stenz
authors.affiliation: Department of Psychiatry, University of Geneva, Switzerland; Department of Basic Neurosciences, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Seblewongel
authors.initials: S
authors.lastname: Zewdie
authors.affiliation: Department of Genetic and Laboratory Medicine, Geneva University Hospital, 1211 Geneva 14, Switzerland.
authors.forename: Térèse
authors.initials: T
authors.lastname: Laforge-Escarra
authors.affiliation: Department of Psychiatry, University of Geneva, Switzerland; Department of Basic Neurosciences, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Julien
authors.initials: J
authors.lastname: Prados
authors.affiliation: Institute of Forensic Medicine, University of Geneva, Switzerland.
authors.forename: Romano
authors.initials: R
authors.lastname: La Harpe
authors.affiliation: Department of Mental Health and Psychiatry, University Hospital of Geneva, Geneva, Switzerland; Department of Basic Neurosciences, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dayer
authors.affiliation: Department of Genetic and Laboratory Medicine, Geneva University Hospital, 1211 Geneva 14, Switzerland.
authors.forename: Ariane
authors.initials: A
authors.lastname: Paoloni-Giacobino
authors.affiliation: Department of Psychiatry, University of Geneva, Switzerland; Department of Mental Health and Psychiatry, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Nader
authors.initials: N
authors.lastname: Perroud
authors.affiliation: Department of Psychiatry, University of Geneva, Switzerland; Department of Mental Health and Psychiatry, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Aubry
mesh_terms: D001344:Autopsy; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism; D001773:Blood Cells / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D012737:Sex Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: BDNF; Epigenetics; Methylation; Prefrontal cortex; Promoter; Quadriceps