Browsing by Author "Traboulsee, Anthony"

Now showing 1 - 1 of 1
  • Thumbnail Image
    Item
    Common variation near IRF6 is associated with IFN-β-induced liver injury in multiple sclerosis
    (Springer Nature, 2018-08) Kowalec, Kaarina; Wright, Galen E.B.; Drögemöller, Britt I.; Aminkeng, Folefac; Bhavsar, Amit P.; Kingwell, Elaine; Yoshida, Eric M.; Traboulsee, Anthony; Marrie, Ruth Ann; Kremenchutzky, Marcelo; Campbell, Trudy L.; Duquette, Pierre; Chalasani, Naga; Wadelius, Mia; Hallberg, Pär; Xia, Zongqi; Jager, Philip L. De; Denny, Joshua C.; Davis, Mary F.; Ross, Colin J.D.; Tremlett, Helen; Carleton, Bruce C.; Medicine, School of Medicine
    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.