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

TY - JOUR

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

AU - Kaur, Simranjeet

AU - Mirza, Aashiq H.

AU - Brorsson, Caroline Anna

AU - Fløyel, Tina

AU - Størling, Joachim

AU - Mortensen, Henrik B.

AU - Pociot, Flemming

AU - Hvidoere International Study Group

N1 - Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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 - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.mce.2015.10.002

DO - 10.1016/j.mce.2015.10.002

M3 - Journal article

C2 - 26450151

SN - 0303-7207

VL - 419

SP - 83

EP - 91

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

ER -