Risk factors for non-responsiveness to 5-aminosalicylic acid in patients with ulcerative colitis identified using retrospective clinical study and Mendelian randomization
Abstract 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 conduc...
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Nature Portfolio
2025-03-01
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| Online Access: | https://doi.org/10.1038/s41598-025-89620-x |
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| author | Zhi-Ning Ye Xin-Tian Liu Yue-Ming Gu Shu-Xian Mao Dan-Hong Liang Kai Zhan Hao-Qiang Lei Shao-Gang Huang |
| author_facet | Zhi-Ning Ye Xin-Tian Liu Yue-Ming Gu Shu-Xian Mao Dan-Hong Liang Kai Zhan Hao-Qiang Lei Shao-Gang Huang |
| author_sort | Zhi-Ning Ye |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
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| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-3e0b9cbf5fc547faa6dcc031b69efb8e2025-08-20T02:51:27ZengNature PortfolioScientific Reports2045-23222025-03-0115111310.1038/s41598-025-89620-xRisk factors for non-responsiveness to 5-aminosalicylic acid in patients with ulcerative colitis identified using retrospective clinical study and Mendelian randomizationZhi-Ning Ye0Xin-Tian Liu1Yue-Ming Gu2Shu-Xian Mao3Dan-Hong Liang4Kai Zhan5Hao-Qiang Lei6Shao-Gang Huang7The Affiliated Dongguan Hospital of Guangzhou University of Chinese MedicineThe Affiliated Dongguan Hospital of Guangzhou University of Chinese MedicineThe Affiliated Dongguan Hospital of Guangzhou University of Chinese MedicineDepartment of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese MedicineThe Affiliated Dongguan Hospital of Guangzhou University of Chinese MedicineThe Affiliated Dongguan Hospital of Guangzhou University of Chinese MedicineHuangpu People’s Hospital of ZhongshanDepartment of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese MedicineAbstract 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.https://doi.org/10.1038/s41598-025-89620-xUlcerative colitis5-Aminosalicylic acidResponsivenessAllergyAspartate aminotransferase-to-alanine aminotransferase ratioInhibitor of nuclear factor kappa-B kinase subunit alpha |
| spellingShingle | Zhi-Ning Ye Xin-Tian Liu Yue-Ming Gu Shu-Xian Mao Dan-Hong Liang Kai Zhan Hao-Qiang Lei Shao-Gang Huang Risk factors for non-responsiveness to 5-aminosalicylic acid in patients with ulcerative colitis identified using retrospective clinical study and Mendelian randomization Scientific Reports Ulcerative colitis 5-Aminosalicylic acid Responsiveness Allergy Aspartate aminotransferase-to-alanine aminotransferase ratio Inhibitor of nuclear factor kappa-B kinase subunit alpha |
| title | Risk factors for non-responsiveness to 5-aminosalicylic acid in patients with ulcerative colitis identified using retrospective clinical study and Mendelian randomization |
| title_full | Risk factors for non-responsiveness to 5-aminosalicylic acid in patients with ulcerative colitis identified using retrospective clinical study and Mendelian randomization |
| title_fullStr | Risk factors for non-responsiveness to 5-aminosalicylic acid in patients with ulcerative colitis identified using retrospective clinical study and Mendelian randomization |
| title_full_unstemmed | Risk factors for non-responsiveness to 5-aminosalicylic acid in patients with ulcerative colitis identified using retrospective clinical study and Mendelian randomization |
| title_short | Risk factors for non-responsiveness to 5-aminosalicylic acid in patients with ulcerative colitis identified using retrospective clinical study and Mendelian randomization |
| title_sort | risk factors for non responsiveness to 5 aminosalicylic acid in patients with ulcerative colitis identified using retrospective clinical study and mendelian randomization |
| topic | Ulcerative colitis 5-Aminosalicylic acid Responsiveness Allergy Aspartate aminotransferase-to-alanine aminotransferase ratio Inhibitor of nuclear factor kappa-B kinase subunit alpha |
| url | https://doi.org/10.1038/s41598-025-89620-x |
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