New genetic biomarkers predicting 5-aminosalicylate-induced adverse events in patients with inflammatory bowel diseases

Abstract

Background: Notably, 5-aminosalicylates (5-ASA) are vital in treating inflammatory bowel diseases (IBD). The adverse events of 5-ASA rarely occur but they could be fatal. Objectives: We aimed to discover new genetic biomarkers predicting 5-ASA-induced adverse events in patients with IBD. Design: This was a retrospective observational study. Methods: We performed a genome-wide association study on patients with IBD in South Korea. We defined subset 1 as 39 all adverse events and 272 controls; subset 2 as 20 severe adverse events and 291 controls (mild adverse events and control); subset 3 as 20 severe adverse events and 272 controls; and subset 4 as 19 mild adverse events and 272 controls. Logistic regression analysis was performed and commonly found associated genes were determined as candidate single-nucleotide polymorphisms predicting 5-ASA adverse events. Results: Patients with Crohn’s disease (CD) were significantly negatively associated with the development of adverse events compared to patients with ulcerative colitis (UC) (5.3% versus 22.9%). However, sex and age at diagnosis were unassociated with the adverse events of 5-ASA. rs13898676 [odds ratio (OR), 20.33; 95% confidence interval (CI), 5.69–72.67; p = 3.57 × e−6], rs12681590 (OR, 7.35; 95% CI, 2.85–19.00; p = 3.78 × e−5), rs10967320 (OR, 4.51; 95% CI, 2.18–9.31; p = 4.72 × e−5), and rs78726924 (OR, 3.54; 95% CI, 1.69–7.40; p = 7.96 × e−5) were genetic biomarkers predicting 5-ASA-induced severe adverse events in patients with IBD. Conclusion: The adverse events of 5-ASA were more common in patients with UC than those with CD in our study. We found that novel rs13898676 nearby WSB2 was the most significant genetic locus contributing to 5-ASA’s adverse event risk.