Gene Variant Linked to Liver Injury Risk in Interferon-Treated MS
Following adjustment for MS disease course, the genome-wide analysis identified an association between chromosome 1q32.2 and IFN-β-induced liver injury.
According to a study published in Nature Genetics, the rs2205986 genetic variant is associated with an increased risk for liver injury among patients with multiple sclerosis (MS) who are treated with interferon-β (IFN-β).
In a 2-stage genome-wide association study, the investigators sought to identify biomarkers predictive of IFN-β-induced liver injury in patients with MS. Study investigators enrolled patients with normal biochemical liver test results prior to IFN-β exposure at baseline. Data from patients with drug-induced liver injury (n=28) were compared with data from controls (n=113) who had normal liver test results and who were exposed to IFN-β therapy for ≥2 years. Whole-genome and human leukocyte antigen-allele imputation was performed for all participants.
Following adjustment for MS disease course, the genome-wide analysis identified an association between chromosome 1q32.2 and IFN-β-induced liver injury (rs2205986[G>A]; odds ratio [OR] 8.5; 95% CI, 3.5-20.4; P =1.9×10–7). In the stage 2 analysis, the 1q32.2 chromosome region (rs2205986) was also significantly associated with IFN-β-induced liver injury (P =.004). Increased levels of aspartate aminotransferase (P =7.6×10–5) and alkaline phosphatase (P =4.9×10–4) were associated with rs2205986. In the 2-stage analysis, rs2205986 surpassed genome-wide significance (OR 8.3; 95% CI, 3.6-19.2; P =2.3 × 10–8).
Limitations of the analysis include its small sample size, which resulted in the identification of only a single pharmacogenomic-related IFN-β-induced liver injury predictor.
Pharmacogenomic testing for rs2205986 prior to “IFN-β therapy, rather than only monitoring liver enzymes during treatment, may prevent [drug-induced liver injury] in at-risk patients.”
Kowalec K, Wright GEB, Drögemöller BI, et al. Common variation near IRF6 is associated with IFN-β-induced liver injury in multiple sclerosis [published online July 16, 2018]. Nat Genet. 2018;50:1081-1085.