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Genes Immun. 2011 Sep;12(6):466-72. doi: 10.1038/gene.2011.18. Epub 2011 Apr 7.

Interferon regulatory factor 5 gene variants and pharmacological and clinical outcome of Interferonβ therapy in multiple sclerosis.

Author information

  • 1VU University Medical Center, Department of Pathology, Amsterdam, The Netherlands. s.vosslamber@vumc.nl

Erratum in

  • Genes Immun. 2012 Jul, 13(5):443. van der PouwKraan, T C T M [corrected to van der Pouw Kraan, TCTM].

Abstract

Interferon-β (IFNβ) therapy is effective in approximately half of the patients with relapsing-remitting multiple sclerosis (RRMS). Clinical non-responders were characterized by an increased expression of IFN response genes before the start of therapy, and a lack of a pharmacologically induced increase in IFN response gene activity. Because Interferon Regulatory Factor 5 (IRF5) is a master regulator of IFN-activity, we carried out a candidate gene study of IRF5 gene variants in relation to the pharmacological and clinical response upon IFNβ treatment. We found that patients with the IRF5 rs2004640-TT and rs47281420-AA genotype exerted a poor pharmacological response to IFNβ compared with patients carrying the respective G-alleles (P=0.0006 and P=0.0023, respectively). Moreover, patients with the rs2004640-TT genotype developed more magnetic resonance imaging (MRI)-based T2 lesions during IFNβ treatment (P=0.003). Accordingly, an association between MRI-based non-responder status and rs2004640-TT genotype was observed (P=0.010). For the rs4728142-AA genotype a trend of an association with more T2 lesions during IFNβ treatment and MRI-based non-responder status was observed (P=0.103 and P=0.154, respectively). The clinical relevance of the rs2004640-TT genotype was validated in an independent cohort wherein a shorter time to first relapse was found (P=0.037). These findings suggest a role for IRF5 gene variation in the pharmacological and clinical outcome of IFNβ therapy that might have relevance as biomarker to predict the response to IFNβ in multiple sclerosis.

PMID:
21471993
[PubMed - indexed for MEDLINE]
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