■值得注意的是,5-氨基水杨酸盐(5-ASA)在治疗炎症性肠病(IBD)中至关重要。5-ASA的不良事件很少发生,但可能是致命的。
■我们旨在发现新的遗传生物标志物,预测IBD患者5-ASA诱导的不良事件。
■这是一项回顾性观察性研究。
■我们对韩国IBD患者进行了全基因组关联研究。我们将子集1定义为39个所有不良事件和272个对照;子集2定义为20个严重不良事件和291个对照(轻度不良事件和对照);子集3定义为20个严重不良事件和272个对照;子集4定义为19个轻度不良事件和272个对照。进行Logistic回归分析,并确定常见的相关基因作为预测5-ASA不良事件的候选单核苷酸多态性。
与溃疡性结肠炎(UC)患者相比,克罗恩病(CD)患者与不良事件的发生显著负相关(5.3%对22.9%)。然而,诊断时的性别和年龄与5-ASA不良事件无关.rs13898676[赔率比(OR),20.33;95%置信区间(CI),5.69-72.67;p=3.57×e-6],rs12681590(或,7.35;95%CI,2.85-19.00;p=3.78×e-5),rs10967320(或,4.51;95%CI,2.18-9.31;p=4.72×e-5),和rs78726924(或,3.54;95%CI,1.69-7.40;p=7.96×e-5)是预测5-ASA诱导的IBD患者严重不良事件的遗传生物标志物。
■在我们的研究中,5-ASA的不良事件在UC患者中比CD患者更常见。我们发现WSB2附近的新型rs13898676是导致5-ASA不良事件风险的最重要的遗传基因座。
UNASSIGNED: 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.
UNASSIGNED: We aimed to discover new genetic biomarkers predicting 5-ASA-induced adverse events in patients with IBD.
UNASSIGNED: This was a retrospective observational study.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.