Document Detail

Assessment of microRNA-related SNP effects in the 3' untranslated region of the IL22RA2 risk locus in multiple sclerosis.
MedLine Citation:
PMID:  24638856     Owner:  NLM     Status:  Publisher    
Recent large-scale association studies have identified over 100 MS risk loci. One of these MS risk variants is single-nucleotide polymorphism (SNP) rs17066096, located ~14 kb downstream of IL22RA2. IL22RA2 represents a compelling MS candidate gene due to the role of IL-22 in autoimmunity; however, rs17066096 does not map into any known functional element. We assessed whether rs17066096 or a nearby proxy SNP may exert pathogenic effects by affecting microRNA-to-mRNA binding and thus IL22RA2 expression using comprehensive in silico predictions, in vitro reporter assays, and genotyping experiments in 6,722 individuals. In silico screening identified two predicted microRNA binding sites in the 3'UTR of IL22RA2 (for hsa-miR-2278 and hsa-miR-411-5p) encompassing a SNP (rs28366) in moderate linkage disequilibrium with rs17066096 (r (2) = 0.4). The binding of both microRNAs to the IL22RA2 3'UTR was confirmed in vitro, but their binding affinities were not significantly affected by rs28366. Association analyses revealed significant association of rs17066096 and MS risk in our independent German dataset (odds ratio  = 1.15, P = 3.48 × 10(-4)), but did not indicate rs28366 to be the cause of this signal. While our study provides independent validation of the association between rs17066096 and MS risk, this signal does not appear to be caused by sequence variants affecting microRNA function.
Christina M Lill; Marcel Schilling; Sara Ansaloni; Julia Schröder; Marian Jaedicke; Felix Luessi; Brit-Maren M Schjeide; Andriy Mashychev; Christiane Graetz; Denis A Akkad; Lisa-Ann Gerdes; Antje Kroner; Paul Blaschke; Sabine Hoffjan; Alexander Winkelmann; Thomas Dörner; Peter Rieckmann; Elisabeth Steinhagen-Thiessen; Ulman Lindenberger; Andrew Chan; Hans-Peter Hartung; Orhan Aktas; Peter Lohse; Mathias Buttmann; Tania Kümpfel; Christian Kubisch; Uwe K Zettl; Joerg T Epplen; Frauke Zipp; Lars Bertram
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-3-18
Journal Detail:
Title:  Neurogenetics     Volume:  -     ISSN:  1364-6753     ISO Abbreviation:  Neurogenetics     Publication Date:  2014 Mar 
Date Detail:
Created Date:  2014-3-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9709714     Medline TA:  Neurogenetics     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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