ARTICLE IN PRESS JID: NEUPSY [m6+;July 16, 2020;16:53] European Neuropsychopharmacology (2020) 000, 1–10 www.elsevier.com/locate/euroneuro Regulation of melanocortin-4-receptor (MC4R) expression by SNP rs17066842 is dependent on glucose concentration Li Qin a , Arun K. Tiwari a,b,c , Clement C. Zai a,b,c , Natalie Freeman a,b , Dongxu Zhai b,c , Fang Liu b,c , Harald Stachelscheid d,e , Philipp Mergenthaler f,g , James L. Kennedy a,b,c , Daniel J. Müller a,b,c,* a Pharmacogenetics Research Clinic, Molecular Brain Science, Centre for Addiction and Mental Health, Toronto M5T 1R8, ON, Canada b Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8, Canada c Department of Psychiatry, University of Toronto, Toronto, Ontario M5T 1R8, Canada d Berlin Institute of Health, Stem Cell Core Facility, 13353 Berlin, Germany e Charité - Universitätsmedizin Berlin, Charité-BIH Centrum Therapy and Research 13353 Berlin, Germany f Charité-Universitätsmedizin Berlin, Department of Experimental Neurology, Department of Neurology, Center for Stroke Research Berlin, 10117 Berlin, Germany g Berlin Institute of Health (BIH), 10178 Berlin, Germany Received 17 July 2019; received in revised form 18 May 2020; accepted 24 May 2020 Available online xxx KEYWORDS MC4R rs17066842; EGR-1; Glucose; Obesity; Type 2 diabetes; Cerebral organoids Abstract Melanocortin-4-receptor (MC4R) gene codes for a G-protein-coupled receptor that is highly ex- pressed in the hypothalamus and involved in the regulation of appetite. Single-nucleotide poly- morphisms (SNPs) in the MC4R gene region have been associated with obesity, type 2-diabetes (T2D) and with antipsychotic-induced weight gain. Of these, rs17066842 (G>A) in the MC4R promoter region is the top variant associated with obesity and diabetes. In this study, we inves- tigated the effect of rs17066842 on MC4R expression at various glucose concentrations using reporter gene expression in the SH-SY5Y cell line and regulation of MC4R expression in human ∗ Corresponding author. E-mail address: daniel.mueller@camh.ca (D.J. Müller). https://doi.org/10.1016/j.euroneuro.2020.05.008 0924-977X/© 2020 Published by Elsevier B.V. Please cite this article as: L. Qin, A.K. Tiwari and C.C. Zai et al., Regulation of melanocortin-4-receptor (MC4R) expression by SNP rs17066842 is dependent on glucose concentration, European Neuropsychopharmacology, https://doi.org/10.1016/j.euroneuro.2020.05. 008