The genetic and regulatory architecture of ERBB3-type 1 diabetes susceptibility locus.
Mol Cell Endocrinol
; 419: 83-91, 2016 Jan 05.
Article
in En
| MEDLINE
| ID: mdl-26450151
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 ß-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 ß-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 ß-cells and may constitute novel targets to prevent ß-cell destruction in T1D.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptor, ErbB-3
/
Polymorphism, Single Nucleotide
/
Diabetes Mellitus, Type 1
Type of study:
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Limits:
Animals
/
Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
Mol Cell Endocrinol
Year:
2016
Document type:
Article
Affiliation country:
Dinamarca