title: Functional characterization of an oxytocin receptor gene variant (rs2268498) previously associated with social cognition by expression analysis in vitro and in human brain biopsy.
abstract: The oxytocin system plays a prominent role in social behavior across species, and numerous genetic studies in humans have reported associations between polymorphisms on the oxytocin receptor (OXTR) gene and phenotypes related to social cognition, affiliation, perspective taking, and sociability in healthy subjects and in patients with atypical social behavior, such as in autism spectrum disorders (ASD). Recently, the first study demonstrating altered agonist-induced OXTR internalization and recycling for the exonic variant rs35062132 emerged. Beside this, there has been no further demonstration of the functionality of the OXTR variants especially there does not exist any for the regulatory units. To address this gap in the literature, we tested the functionality of the promoter flanking single nucleotide polymorphism (SNP) rs2268498, which has proven an interesting candidate for predicting social behavior in recent association studies. Results of genetic expression analyses in human hippocampal tissue showed a twofold difference in messenger RNA transcription, dependent on the presence or absence of the C-allele. This finding was corroborated by cloning, i.e., in vitro reporter gene expression analysis after transfection of OXTR promoter plasmids into HEK-293 cells. Our results underline the importance of OXTR rs2268498 for genetic research in social behavior and ASD.
authors.affiliation: a Department of Psychology, Laboratory of Neurogenetics , University of Bonn , Bonn , Germany.|b Center for Economics & Neuroscience , University of Bonn , Bonn , Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Reuter
authors.affiliation: c Institute of Psychology and Education , Ulm University , Ulm , Germany.|d Key Laboratory for NeuroInformation/Center for Information in Medicine, School of Life Science and Technology , University of Electronic Science and Technology of China , Chengdu , China.
authors.forename: Christian
authors.initials: C
authors.lastname: Montag
authors.affiliation: e Institute of Economics , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Altmann
authors.affiliation: f Department of Epileptology , University Hospital of Bonn , Bonn , Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Bendlow
authors.affiliation: f Department of Epileptology , University Hospital of Bonn , Bonn , Germany.|g Department of NeuroCognition , Life & Brain Center , Bonn , Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Elger
authors.affiliation: h Department of Psychiatry, Central Institute of Mental Health Mannheim , University of Heidelberg , Heidelberg , Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kirsch
authors.affiliation: i Department of Neuropathology , University Hospital of Bonn , Bonn , Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Becker
authors.affiliation: i Department of Neuropathology , University Hospital of Bonn , Bonn , Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schoch-McGovern
authors.affiliation: j Department of Neurosurgery , University Hospital of Bonn , Bonn , Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Simon
authors.affiliation: b Center for Economics & Neuroscience , University of Bonn , Bonn , Germany.|f Department of Epileptology , University Hospital of Bonn , Bonn , Germany.|g Department of NeuroCognition , Life & Brain Center , Bonn , Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Weber
authors.affiliation: a Department of Psychology, Laboratory of Neurogenetics , University of Bonn , Bonn , Germany.|b Center for Economics & Neuroscience , University of Bonn , Bonn , Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Felten
mesh_terms: D001706:Biopsy; D003071:Cognition / Q000502:physiology; D004827:Epilepsy / Q000378:metabolism / Q000473:pathology; D057809:HEK293 Cells; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000235:genetics* / Q000378:metabolism*; D012938:Social Perception; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: C569600:OXTR protein, human; D012333:RNA, Messenger; D018045:Receptors, Oxytocin
keywords: Oxytocin receptor; functionality; mRNA expression; rs2268498; social behavior