Common variation near IRF6 is associated with IFN-β-induced liver injury in multiple sclerosis View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-08

AUTHORS

Kaarina Kowalec, Galen E. B. Wright, Britt I. Drögemöller, Folefac Aminkeng, Amit P. Bhavsar, Elaine Kingwell, Eric M. Yoshida, Anthony Traboulsee, Ruth Ann Marrie, Marcelo Kremenchutzky, Trudy L. Campbell, Pierre Duquette, Naga Chalasani, Mia Wadelius, Pär Hallberg, Zongqi Xia, Philip L. De Jager, Joshua C. Denny, Mary F. Davis, Colin J. D. Ross, Helen Tremlett, Bruce C. Carleton

ABSTRACT

Multiple sclerosis (MS) is a disease of the central nervous system treated with disease-modifying therapies, including the biologic, interferon-β (IFN-β). Up to 60% of IFN-β-exposed MS patients develop abnormal biochemical liver test results1,2, and 1 in 50 experiences drug-induced liver injury3. Since genomic variation contributes to other forms of drug-induced liver injury4,5, we aimed to identify biomarkers of IFN-β-induced liver injury using a two-stage genome-wide association study. The rs2205986 variant, previously linked to differential expression of IRF6, surpassed genome-wide significance in the combined two-stage analysis (P = 2.3 × 10-8, odds ratio = 8.3, 95% confidence interval = 3.6-19.2). Analysis of an independent cohort of IFN-β-treated MS patients identified via electronic medical records showed that rs2205986 was also associated with increased peak levels of aspartate aminotransferase (P = 7.6 × 10-5) and alkaline phosphatase (P = 4.9 × 10-4). We show that these findings may be applicable to predicting IFN-β-induced liver injury, offering insight into its safer use. More... »

PAGES

1081-1085

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-018-0168-y

    DOI

    http://dx.doi.org/10.1038/s41588-018-0168-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1105584568

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30013178


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