title: Methylation of the oxytocin receptor gene in clinically depressed patients compared to controls: The role of OXTR rs53576 genotype.
abstract: The emerging field of epigenetics provides a biological basis for gene-environment interactions relevant to depression. We focus on DNA methylation of exon 1 and 2 of the oxytocin receptor gene (OXTR) promoter. The research aims of the current study were to compare OXTR DNA methylation of depressed patients with healthy control subjects and to investigate possible influences of the OXTR rs53576 genotype. The sample of the present study consisted of 43 clinically depressed women recruited from a psychosomatic inpatient unit and 42 healthy, female control subjects - mean age 30 years (SD = 9). DNA methylation profiles of the OXTR gene were assessed from leukocyte DNA by means of bisulfite sequencing. Depressed female patients had decreased OXTR exon 1 DNA methylation compared to non-depressed women. The association between depression and methylation level was moderated by OXTR rs53576 genotype. Exon 2 methylation was associated with OXTR rs53576 genotype but not with depression. Our findings suggest exon-specific methylation mechanisms. Exon 1 methylation appears to be associated with depressive phenotypes whereas exon 2 methylation is influenced by genotype. Previously reported divergent associations between OXTR genotype and depression might be explained by varying exon 1 methylation. In order to further understand the etiology of depression, research on the interplay between genotype, environmental influences and exon-specific methylation patterns is needed.
authors.affiliation: Department of Psychosomatic Medicine and Psychotherapy, University Medical Center, Mainz, Germany. Electronic address: iris.reiner@unimedizin-mainz.de.
authors.forename: I
authors.initials: I
authors.lastname: Reiner
authors.affiliation: Center for Child and Family Studies, Rommert Casimir Institute for Developmental Psychopathology, Leiden University, Leiden, The Netherlands.
authors.forename: M H
authors.initials: MH
authors.lastname: Van IJzendoorn
authors.affiliation: Center for Child and Family Studies, Rommert Casimir Institute for Developmental Psychopathology, Leiden University, Leiden, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Bakermans-Kranenburg
authors.affiliation: Molecular Neuroscience Laboratory, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Bleich
authors.affiliation: Department of Psychosomatic Medicine and Psychotherapy, University Medical Center, Mainz, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Beutel
authors.affiliation: Molecular Neuroscience Laboratory, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Frieling
mesh_terms: D000328:Adult; D019175:DNA Methylation / Q000235:genetics*; D003863:Depression / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018045:Receptors, Oxytocin / Q000235:genetics*
chemical_list: C569600:OXTR protein, human; D018045:Receptors, Oxytocin
keywords: Biomarkers; Depression; Exon-specific; Methylation; OXTR; Oxytocin