Nature genetics · 2018
Common variation near IRF6 is associated with IFN-β-induced liver injury in multiple sclerosis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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, De Jager Philip L, Denny Joshua C, Davis Mary F, Ross Colin J D, Tremlett Helen, Carleton Bruce C
Аннотация
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.