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

TitleCommon variation near IRF6 is associated with IFN-β-induced liver injury in multiple sclerosis.
Publication TypeJournal Article
Year of Publication2018
AuthorsKowalec K, Wright GEB, Drögemöller BI, Aminkeng F, Bhavsar AP, Kingwell E, Yoshida EM, Traboulsee A, Marrie RAnn, Kremenchutzky M, Campbell TL, Duquette P, Chalasani N, Wadelius M, Hallberg P, Xia Z, De Jager PL, Denny JC, Davis MF, Ross CJD, Tremlett H, Carleton BC
JournalNat Genet
Volume50
Issue8
Pagination1081-1085
Date Published09/2018
ISSN1546-1718
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 results, and 1 in 50 experiences drug-induced liver injury. Since genomic variation contributes to other forms of drug-induced liver injury, 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, 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) and alkaline phosphatase (P = 4.9 × 10). We show that these findings may be applicable to predicting IFN-β-induced liver injury, offering insight into its safer use.

DOI10.1038/s41588-018-0168-y
Alternate JournalNat. Genet.
PubMed ID30013178