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

Jong, V.M. de; Zaldumbide, A.; Slik, A.R. van der; Persengiev, S.P.; Roep, B.O.; Koeleman, B.P.C. (2013)

Article / Letter to editor

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.

• All authors: Jong, V.M. de; Zaldumbide, A.; Slik, A.R. van der; Persengiev, S.P.; Roep, B.O.; Koeleman, B.P.C.
• Date: 2013-01-28
• Journal: Genes and Immunity
• Volume: 14
• Issue: 1
• Pages: 58 - 61
• DOI: doi:10.1038/gene.2012.38