Journal
GENES AND IMMUNITY
Volume 14, Issue 1, Pages 58-61Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gene.2012.38
Keywords
microRNA; type 1 diabetes; rare variants; post-transcriptional control
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Funding
- Dutch Diabetes Research Foundation, The Netherlands
- Juvenile Diabetes Research Foundation
- Leiden University Medical Center
- European Commission
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The genetic variation causal for predisposition to type 1 diabetes (T1D) remains unidentified for the majority of known T1D risk loci. MicroRNAs function as post-transcriptional gene regulators by targeting microRNA-binding sites in the 3' untranslated regions (UTR) of mRNA. Genetic variation within the 3'-UTR of T1D-associated genes may contribute to T1D development by altering microRNA-mediated gene regulation. In silico analysis of variable sites predicted altered microRNA binding in established T1D loci. Functional implications were assessed for variable sites in the 3'-UTR of T1D candidate risk genes CTLA4 and IL10, both involved in immune regulation. We confirmed that in these genes 3'-UTR variation either disrupted or introduced a microRNA-binding site, affecting the repressive capacity of miR-302a* and miR-523, respectively. Our study points to the potential of 3'-UTR variation to affect T1D pathogenesis by altering post-transcriptional gene regulation by microRNAs. Genes and Immunity (2013) 14, 58-61; doi: 10.1038/gene.2012.38; published online 30 August 2012
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