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.
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Authors | S Vosslamber, L F van der Voort, I J van den Elskamp, R Heijmans, C Aubin, B M J Uitdehaag, J B A Crusius, T C T M van der Pouw Kraan, T C T M van der PouwKraan, M Comabella, X Montalban, D A Hafler, P L De Jager, J Killestein, C H Polman, C L Verweij |
Journal | Genes and immunity
(Genes Immun)
Vol. 12
Issue 6
Pg. 466-72
(Sep 2011)
ISSN: 1476-5470 [Electronic] England |
PMID | 21471993
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- IRF5 protein, human
- Interferon Regulatory Factors
- Interferon-beta
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Topics |
- Adult
- Biomarkers
- Cohort Studies
- Female
- Gene Expression
- Genetic Variation
- Genotype
- Humans
- Interferon Regulatory Factors
(genetics)
- Interferon-beta
(pharmacology, therapeutic use)
- Magnetic Resonance Imaging
- Male
- Multiple Sclerosis, Relapsing-Remitting
(drug therapy, genetics)
- Polymorphism, Single Nucleotide
- Treatment Outcome
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