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Review
. 2019 Mar 19;19(5):20.
doi: 10.1007/s11892-019-1141-6.

Genetic Mechanisms Highlight Shared Pathways for the Pathogenesis of Polygenic Type 1 Diabetes and Monogenic Autoimmune Diabetes

Matthew B Johnson  1 , Karen Cerosaletti  2 , Sarah E Flanagan  3 , Jane H Buckner  2
Affiliations
Review

Genetic Mechanisms Highlight Shared Pathways for the Pathogenesis of Polygenic Type 1 Diabetes and Monogenic Autoimmune Diabetes

Matthew B Johnson et al. Curr Diab Rep. .

Abstract

Purpose of review: To highlight pathways important for the development of autoimmune diabetes by investigating shared mechanisms of disease in polygenic and monogenic diabetes.

Recent findings: Genome-wide association studies have identified 57 genetic risk loci for type 1 diabetes. Progress has been made in unravelling the mechanistic effects of some of these variants, providing key insights into the pathogenesis of type 1 diabetes. Seven monogenic disorders have also been described where diabetes features as part of an autoimmune syndrome. Studying these genes in relation to polygenic risk loci provides a unique opportunity to dissect pathways important for the development of immune-mediated diabetes. Monogenic autoimmune diabetes can result from the dysregulation of multiple pathways suggesting that small effects on many immune processes are required to drive the autoimmune attack on pancreatic beta cells in polygenic type 1 diabetes. A breakdown in central and peripheral immune tolerance is a common theme in the genetic mechanisms of both monogenic and polygenic disease which highlights the importance of these checkpoints in the development and treatment of islet autoimmunity.

Keywords: Autoimmunity; Immune tolerance; Monogenic diabetes; Polygenic risk.

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Conflict of interest statement

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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