Ye Zhi-Ning, Liu Xin-Tian, Gu Yue-Ming, Mao Shu-Xian, Liang Dan-Hong, Zhan Kai, Lei Hao-Qiang, Huang Shao-Gang
The Affiliated Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan, China.
The Ninth Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan, China.
Sci Rep. 2025 Mar 17;15(1):9182. doi: 10.1038/s41598-025-89620-x.
This study aimed to identify risk factors and potential targets associated with non-responsiveness to 5-Aminosalicylic acid (5-ASA) in patients with ulcerative colitis (UC). Patients with mild to moderate UC were grouped based on their responsiveness to 5-ASA. Regression analysis was conducted to identify risk factors for non-responsiveness, while Mendelian randomization (MR) analysis was used to evaluate the potential targets. Among 50 patients (11 non-responders and 39 responders), non-responders exhibited higher incidences of fever, back pain, allergy history, and ankylosing spondylitis, as well as elevated monocyte count and alanine aminotransferase (ALT) level, but a lower aspartate aminotransferase-to-ALT (AST/ALT) ratio (all P < 0.05). Allergy history was a risk factor (OR 140.50, P = 0.021), while a high AST/ALT ratio was a protective factor (OR 0.001, P = 0.023) for non-responsiveness. The area under the receiver operating characteristic curve for the AST/ALT ratio was 0.80. MR analysis showed that inhibition of the inhibitor of nuclear factor kappa-B kinase subunit alpha (CHUK) by 5-ASA, targeting ALT, increased the risk of UC (OR 1.02, P = 0.002). Our findings suggested that allergy history and the AST/ALT ratio were associated with non-responsiveness to 5-ASA, and CHUK was identified as a potential target for ALT-related non-responsiveness.Trial Registration: ChiCTR2400084086|| http://www.chictr.org.cn/ , Chinese Clinical Trial Registry, 2024-05-10.
本研究旨在确定溃疡性结肠炎（UC）患者对5-氨基水杨酸（5-ASA）无反应的相关危险因素和潜在靶点。轻度至中度UC患者根据其对5-ASA的反应进行分组。进行回归分析以确定无反应的危险因素，同时使用孟德尔随机化（MR）分析来评估潜在靶点。在50例患者（11例无反应者和39例反应者）中，无反应者发热、背痛、过敏史和强直性脊柱炎的发生率较高，单核细胞计数和丙氨酸氨基转移酶（ALT）水平升高，但天冬氨酸氨基转移酶与ALT之比（AST/ALT）较低（所有P<0.05）。过敏史是无反应的危险因素（OR 140.50，P=0.021），而高AST/ALT比是无反应的保护因素（OR 0.001，P=0.023）。AST/ALT比的受试者工作特征曲线下面积为0.80。MR分析表明，5-ASA靶向ALT抑制核因子κB激酶亚基α（CHUK）的抑制剂会增加UC的风险（OR 1.02，P=0.002）。我们的研究结果表明，过敏史和AST/ALT比与对5-ASA无反应有关，并且CHUK被确定为ALT相关无反应的潜在靶点。试验注册：ChiCTR2400084086|| http://www.chictr.org.cn/ ，中国临床试验注册中心，2024年5月10日。
