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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 4/2013

Open Access 01-08-2013 | Research article

Identification of three new cis-regulatory IRF5 polymorphisms: in vitro studies

Authors: Elisa Alonso-Perez, Romina Fernandez-Poceiro, Emilie Lalonde, Tony Kwan, Manuel Calaza, Juan J Gomez-Reino, Jacek Majewski, Antonio Gonzalez

Published in: Arthritis Research & Therapy | Issue 4/2013

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Abstract

Background

Polymorphisms in the interferon regulatory factor 5 (IRF5) gene are associated with susceptibility to systemic lupus erythematosus, rheumatoid arthritis and other diseases through independent risk and protective haplotypes. Several functional polymorphisms are already known, but they do not account for the protective haplotypes that are tagged by the minor allele of rs729302.

Methods

Polymorphisms in linkage disequilibrium (LD) with rs729302 or particularly associated with IRF5 expression were selected for functional screening, which involved electrophoretic mobility shift assays (EMSAs) and reporter gene assays.

Results

A total of 54 single-nucleotide polymorphisms in the 5' region of IRF5 were genotyped. Twenty-four of them were selected for functional screening because of their high LD with rs729302 or protective haplotypes. In addition, two polymorphisms were selected for their prominent association with IRF5 expression. Seven of these twenty-six polymorphisms showed reproducible allele differences in EMSA. The seven were subsequently analyzed in gene reporter assays, and three of them showed significant differences between their two alleles: rs729302, rs13245639 and rs11269962. Haplotypes including the cis-regulatory polymorphisms correlated very well with IRF5 mRNA expression in an analysis based on previous data.

Conclusion

We have found that three polymorphisms in LD with the protective haplotypes of IRF5 have differential allele effects in EMSA and in reporter gene assays. Identification of these cis-regulatory polymorphisms will allow more accurate analysis of transcriptional regulation of IRF5 expression, more powerful genetic association studies and deeper insight into the role of IRF5 in disease susceptibility.
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Metadata
Title
Identification of three new cis-regulatory IRF5 polymorphisms: in vitro studies
Authors
Elisa Alonso-Perez
Romina Fernandez-Poceiro
Emilie Lalonde
Tony Kwan
Manuel Calaza
Juan J Gomez-Reino
Jacek Majewski
Antonio Gonzalez
Publication date
01-08-2013
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 4/2013
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar4262

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