R150S mutation in the human oxytocin receptor: Gain-of-function effects and implication in autism spectrum disorder.

Autor: Liu X; Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Cherepanov S; Research Center for Child Mental Development, Kanazawa University, Kanazawa, Kanazawa, Ishikawa, Japan; Division of Socio-Cognitive-Neuroscience, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Kanazawa, Japan; Institute for Functional Genomics, French National Centre for Scientific Research, Montpellier, Occitanie, France., Abouzari M; Department of Otolaryngology-Head and Neck Surgery, University of California, Irvine, CA 92697, USA., Zuko A; Department of Molecular Neurobiology, Donders Institute for Brain, Cognition and Behaviour and Faculty of Science, Radboud University, Nijmegen, the Netherlands., Yang S; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, USA., Sayadi J; Stanford University School of Medicine, Palo Alto, CA, USA., Jia X; Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen, China., Terao C; Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan; The Department of Applied Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan., Sasaki T; Department of Physical and Health Education, Graduate School of Education, The University of Tokyo, Tokyo, Japan., Yokoyama S; Research Center for Child Mental Development, Kanazawa University, Kanazawa, Kanazawa, Ishikawa, Japan; Division of Socio-Cognitive-Neuroscience, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Kanazawa, Japan. Electronic address: shigeruy@med.kanazawa-u.ac.jp.
Jazyk: angličtina
Zdroj: Peptides [Peptides] 2024 Dec; Vol. 182, pp. 171301. Date of Electronic Publication: 2024 Oct 10.
DOI: 10.1016/j.peptides.2024.171301
Abstrakt: This study investigates the rs547238576 (R150S) missense variant in the oxytocin receptor (OXTR) gene, previously observed through screening of rare variants in Japanese individuals with autism spectrum disorders (ASD). Contrary to the anticipated loss-of-function, R150S exhibits gain-of-function effects, enhancing oxytocin (OXT) sensitivity, ligand-binding affinity, and OXT-induced Ca 2+ mobilization in vitro. This suggests R150S may alter OXT signaling, potentially contributing to the excitatory/inhibitory imbalance seen in ASD and other psychiatric disorders. Our findings underscore the significance of genetic variations in OXTR on functional activity and highlight the necessity for population-specific genetic study and in vitro analysis to elucidate genetic susceptibilities to neuropsychiatric conditions.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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