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

par Kaur, Simranjeet;Mirza, Aashiq Hussain;Brorsson, Caroline;Fløyel, Tina;Størling, Joachim;Mortensen, Henrik Bindesbøl;Pociot, Flemming;Aanstoot, Henk Jan;De Beaufort, Carine;Cameron, Fiona;Castano, Luis Antonio;Dorchy, Harry ;Fisher, Lynda;Kaprio, Eero;Lange, Karin K.S.;Neu, Andreas;Njølstad, Pål Rasmus;Phillip, Moshe;Robert, Jean-Jacques ;Urukami, Tatsuhiko;Barrett, Timothy Geoffrey;Chiarelli, Francesco;Danne, Thomas;Hoey, Hilary;Kocova, Mirjana;Schoenle, Eugen;Swift, Peter G.F.;Vanelli, Maurizio
Référence Molecular and cellular endocrinology, 419, page (83-91)
Publication Publié, 2016-01

Article révisé par les pairs

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Résumé :

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.