Reference : The genetic and regulatory architecture of ERBB3-type 1 diabetes susceptibility locus

	Document type :	Scientific journals : Article
	Discipline(s) :	Human health sciences : Multidisciplinary, general & others
	To cite this reference:	http://hdl.handle.net/10993/27173

Title :	The genetic and regulatory architecture of ERBB3-type 1 diabetes susceptibility locus
Language :	English
Author, co-author :	Kaur, S. [Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Pediatrics, Herlev University Hospital, Herlev Ringvej 75, Herlev, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark]
	Mirza, A. H. [Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Pediatrics, Herlev University Hospital, Herlev Ringvej 75, Herlev, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark, Center for Non-coding RNA in Technology and Health, University of Copenhagen, Denmark]
	Brorsson, C. A. [Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Pediatrics, Herlev University Hospital, Herlev Ringvej 75, Herlev, Denmark]
	Fløyel, T. [Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Pediatrics, Herlev University Hospital, Herlev Ringvej 75, Herlev, Denmark]
	Størling, J. [Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Pediatrics, Herlev University Hospital, Herlev Ringvej 75, Herlev, Denmark]
	Mortensen, H. B. [Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Pediatrics, Herlev University Hospital, Herlev Ringvej 75, Herlev, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark]
	Pociot, F. [Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Pediatrics, Herlev University Hospital, Herlev Ringvej 75, Herlev, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark, Center for Non-coding RNA in Technology and Health, University of Copenhagen, Denmark]
	Aanstoot, H.-J. [Center for Pediatric and Adolescent Diabetes Care and Research, Rotterdam, Netherlands]
	De Beaufort, Carine [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
	Cameron, F. [Department of Endocrinology and Diabetes, Royal Children's Hospital, Parkville, VIC, Australia]
	Castano, L. [Endocrinology and Diabetes Research Group, Hospital de Cruces, University of Basque Country, Barakaldo, Spain]
	Dorchy, H. [Diabetology Clinic, University Hospital Reine Fabiola, Brussels, Belgium]
	Fisher, L. [Department of Endocrinology and Diabetes Children's Hospital of Los Angeles, Los Angeles, CA, United States]
	Kaprio, E. [Department of Paediatrics, Peijas Hospital, HUS, Finland]
	Lange, K. [Department of Medical Psychology, Hannover Medical School, Hannover, Germany]
	Neu, A. [Clinic for Children and Adolescence, University of Tuebingen, Tuebingen, Germany]
	Njolstad, P. R. [Department of Clinical Medicine University of Bergen, Bergen, Norway, Department of Paediatrics, Haukeland University Hospital, Bergen, Norway]
	Phillip, M. [National Center of Childhood Diabetes, Schneiders Medical Center of Israel, Petah Tikva, Israel]
	Urukami, T. [School of Medicine, Nihon University, Tokyo, Japan]
	Barrett, T. [Institute of Child Health and Birmingham Children's Hospital, University of Birmingham, Birmingham, United Kingdom]
	Chiarelli, F. [Clinica Pediatrica, Ospedale Policlinico, Chieti, Italy]
	Danne, T. [Kinderkrankenhaus auf der Bult, Hannover, Germany]
	Hoey, H. [University of Dublin, National Children's Hospital, Tallaght, Ireland]
	Kocova, M. [Pediatric Clinic-Skopje, Macedonia]
	Mortensen, B. [Department of Pediatrics, Herlev Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark]
	Schoenle, J. [University Children's Hospital, Zurich, Switzerland]
	Swift, G. F. [Leicester Royal Infirmary Childrens Hospital, Leicester, United Kingdom]
	Vanelli, M. [Clinica Pediatrica, Centro di Diabetologia, Parma, Italy]
	Åman, J. [Örebro Medical Centre Hospital, Department of Paediatrics, Sweden]
	Robert, J.J. []
Publication date :	2016
Journal title :	Molecular and Cellular Endocrinology
Publisher :	Elsevier Ireland Ltd
Volume :	419
Pages :	83-91
Peer reviewed :	Yes (verified by ORBilu)
ISSN :	03037207
Keywords :	[en] Apoptosis ; Beta cell ; CTCF ; ERBB3 ; LncRNAs ; Type 1 diabetes ; Article ; B lymphocyte ; ERBB3 gene
Abstract :	[en] The study aimed to explore the role of ERBB3 in type 1 diabetes (T1D). We examined whether genetic variation of ERBB3 (rs2292239) affects residual β-cell function in T1D cases. Furthermore, we examined the expression of ERBB3 in human islets, the effect of ERBB3 knockdown on apoptosis in insulin-producing INS-1E cells and the genetic and regulatory architecture of the ERBB3 locus to provide insights to how rs2292239 may confer disease susceptibility. rs2292239 strongly correlated with residual β-cell function and metabolic control in children with T1D. ERBB3 locus associated lncRNA (NONHSAG011351) was found to be expressed in human islets. ERBB3 was expressed and down-regulated by pro-inflammatory cytokines in human islets and INS-1E cells; knockdown of ERBB3 in INS-1E cells decreased basal and cytokine-induced apoptosis. Our data suggests an important functional role of ERBB3 and its potential regulators in the β-cells and may constitute novel targets to prevent β-cell destruction in T1D. © 2015 Elsevier Ireland Ltd.
Permalink :	http://hdl.handle.net/10993/27173
DOI :	10.1016/j.mce.2015.10.002

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