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

Hvidoere International Study Group

doi:10.1016/j.mce.2015.10.002

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

Hvidoere International Study Group

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	83-91
Number of pages	9
Journal	Molecular and Cellular Endocrinology
Volume	419
DOIs	https://doi.org/10.1016/j.mce.2015.10.002
State	Published - 5 Jan 2016
Externally published	Yes

Funding

Funders	Funder number
European Foundation
National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases	DP3DK085678
Strategiske Forskningsråd	09-067036/DSF
Københavns Universitet
Poul og Erna Sehested Hansens Fond

Keywords

Apoptosis
Beta cell
CTCF
ERBB3
LncRNAs
Type 1 diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.mce.2015.10.002

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title = "The genetic and regulatory architecture of ERBB3-type 1 diabetes susceptibility locus",

abstract = "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.",

keywords = "Apoptosis, Beta cell, CTCF, ERBB3, LncRNAs, Type 1 diabetes",

author = "{Hvidoere International Study Group} and Simranjeet Kaur and Mirza, {Aashiq H.} and Brorsson, {Caroline A.} and Tina Fl{\o}yel and Joachim St{\o}rling and Mortensen, {Henrik B.} and Flemming Pociot and Aanstoot, {Henk Jan} and {de Beaufort}, {Carine E.} and Fergus Cameron and Luis Castano and Harry Dorchy and Lynda Fisher and Eero Kaprio and Karin Lange and Andreas Neu and Njolstad, {Pal R.} and Moshe Phillip and Jean Robert and Tatsuhiko Urukami and Tim Barrett and Francesco Chiarelli and Thomas Danne and Hilary Hoey and Mirjana Kocova and Henrik Mortensen and Eugen Schoenle and Swift, {Peter F.} and Maurizio Vanelli and Jan {\AA}man",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Ireland Ltd.",

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doi = "10.1016/j.mce.2015.10.002",

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T1 - The genetic and regulatory architecture of ERBB3-type 1 diabetes susceptibility locus

AU - Hvidoere International Study Group

AU - Kaur, Simranjeet

AU - Mirza, Aashiq H.

AU - Brorsson, Caroline A.

AU - Fløyel, Tina

AU - Størling, Joachim

AU - Mortensen, Henrik B.

AU - Pociot, Flemming

AU - Aanstoot, Henk Jan

AU - de Beaufort, Carine E.

AU - Cameron, Fergus

AU - Castano, Luis

AU - Dorchy, Harry

AU - Fisher, Lynda

AU - Kaprio, Eero

AU - Lange, Karin

AU - Neu, Andreas

AU - Njolstad, Pal R.

AU - Phillip, Moshe

AU - Robert, Jean

AU - Urukami, Tatsuhiko

AU - Barrett, Tim

AU - Chiarelli, Francesco

AU - Danne, Thomas

AU - Hoey, Hilary

AU - Kocova, Mirjana

AU - Mortensen, Henrik

AU - Schoenle, Eugen

AU - Swift, Peter F.

AU - Vanelli, Maurizio

AU - Åman, Jan

PY - 2016/1/5

Y1 - 2016/1/5

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Beta cell

KW - CTCF

KW - ERBB3

KW - LncRNAs

KW - Type 1 diabetes

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SN - 0303-7207

VL - 419

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EP - 91

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

ER -

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

Abstract

Funding

Keywords

UN SDGs

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