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Current Diabetes Reports
Published in: Current Diabetes Reports 11/2015

01-11-2015 | Pathogenesis of Type 1 Diabetes (A Pugliese, Section Editor)

Effects of Type 1 Diabetes-Associated IFIH1 Polymorphisms on MDA5 Function and Expression

Authors: Benjamin M. Looney, Chang-Qing Xia, Patrick Concannon, David A. Ostrov, Michael J. Clare-Salzler

Published in: Current Diabetes Reports | Issue 11/2015

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Abstract

Recent evidence has highlighted the role of the innate immune system in type 1 diabetes (T1D) pathogenesis. Specifically, aberrant activation of the interferon response prior to seroconversion of T1D-associated autoantibodies supports a role for the interferon response as a precipitating event toward activation of autoimmunity. Melanoma differentiation-associated protein 5 (MDA5), encoded by IFIH1, mediates the innate immune system’s interferon response to certain viral species that form double-stranded RNA (dsRNA), the MDA5 ligand, during their life cycle. Extensive research has associated single nucleotide polymorphisms (SNPs) within the coding region of IFIH1 with T1D. This review discusses the different risk and protective IFIH1 alleles in the context of recent structural and functional analysis that relate to MDA5 regulation of interferon responses. These studies have provided a functional hypothesis for IFIH1 T1D-associated SNPs’ effects on MDA5-mediated interferon responses as well as supporting the genome-wide association (GWA) studies that first associated IFIH1 with T1D.
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Metadata
Title
Effects of Type 1 Diabetes-Associated IFIH1 Polymorphisms on MDA5 Function and Expression
Authors
Benjamin M. Looney
Chang-Qing Xia
Patrick Concannon
David A. Ostrov
Michael J. Clare-Salzler
Publication date
01-11-2015
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 11/2015
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-015-0656-8

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