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

被引：30

作者：

de Jong, V. M. ^{[1
]}

Zaldumbide, A. ^{[2
]}

van der Slik, A. R. ^{[1
]}

Persengiev, S. P. ^{[3
]}

Roep, B. O. ^{[1
]}

Koeleman, B. P. C. ^{[3
]}

机构：

[1] Leiden Univ Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands

[2] Leiden Univ Med Ctr, Dept Mol Cell Biol, Leiden, Netherlands

[3] Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 Utrecht, Netherlands

来源：

GENES AND IMMUNITY | 2013年 / 14卷 / 01期

关键词：

microRNA; type; 1; diabetes; rare variants; post-transcriptional control; SINGLE-NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE ASSOCIATION; MICRORNA TARGET SITES; RECENT-ONSET; METAANALYSIS; DISEASES; LOCI;

D O I：

10.1038/gene.2012.38

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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

引用

页码：58 / 61

页数：4

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