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Post-transcriptional control of candidate risk genes for type 1 diabetes by rare genetic variants

Genes & Immunity volume 14, pages 58–61 (2013)Cite this article

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Abstract

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.

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Acknowledgements

This work was funded by grants from the Dutch Diabetes Research Foundation, The Netherlands, The Juvenile Diabetes Research Foundation, The Leiden University Medical Center and the 7th Framework Program of the European Commission.

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Authors and Affiliations

  1. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands

    V M de Jong, A R van der Slik & B O Roep

  2. Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands

    A Zaldumbide

  3. Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands

    S P Persengiev & B P C Koeleman

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  1. V M de Jong
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Correspondence to B P C Koeleman.

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de Jong, V., Zaldumbide, A., van der Slik, A. et al. Post-transcriptional control of candidate risk genes for type 1 diabetes by rare genetic variants. Genes Immun 14, 58–61 (2013). https://doi.org/10.1038/gene.2012.38

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