Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Feb 16, 2024; 12(5): 891-902
Published online Feb 16, 2024. doi: 10.12998/wjcc.v12.i5.891
Serum urate is associated with an increased risk of inflammatory bowel disease: A bidirectional Mendelian randomization study
Song Zhang, Xue Fang, Le Kang, Xiang-Yu Sui, Miao Liu, Yu-Jia Luo, Shuo Fu, Zhao-Shen Li, Sheng-Bing Zhao, Yu Bai
Song Zhang, Xue Fang, Le Kang, Xiang-Yu Sui, Miao Liu, Yu-Jia Luo, Shuo Fu, Yu Bai, Department of Gastroenterology, Changhai Hospital, Shanghai 200433, China
Zhao-Shen Li, Sheng-Bing Zhao, Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai 200433, China
Zhao-Shen Li, Sheng-Bing Zhao, Digestive Endoscopy Center, Changhai Hospital, Naval/Second Military Medical University, Shanghai 200433, China
Zhao-Shen Li, Sheng-Bing Zhao, National Clinical Research Center for Digestive Diseases, Shanghai 200433, China
Co-first authors: Song Zhang and Xue Fang.
Co-corresponding authors: Sheng-Bing Zhao and Yu Bai.
Author contributions: Zhang S, Zhao SB and Bai Y designed the research; Zhang S, Kang L and Luo YJ performed the research; Zhang S, Fang X, Kang L and Luo YJ analyzed the data; Sui XY, Liu M and Fu S visualized the data; Zhang S, Fang X, Kang L, Sui XY, Zhao SB and Bai Y wrote the paper; Fang X, Zhao S and Bai Y received the funding; Li ZS, Zhao SB and Bai Y supervised the research.
Supported by National Natural Science Foundation of China, No. 82170567, No. 81873546, No. 82170568, and No. 82300627; Program of Shanghai Academic/Technology Research Leader, No. 22XD1425000; The "Shu Guang" project of Shanghai Municipal Education Commission and Shanghai Education Development Foundation, No. 19SG30, China; Deep Blue Project of Naval Medical University (Pilot Talent Plan); The Chenguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission, No. 22CGA42; The Shanghai Sailing Program, No. 23YF1458600; and Shanghai Natural Science Foundation, No. 23ZR1478700.
Institutional review board statement: The study did not include human trials.
Institutional animal care and use committee statement: All animal experimental procedures were approved and conducted in accordance with the guidelines of the Animal Care Committee of Navy Medical University (CHEC(A.E.)2023-046).
Informed consent statement: All data used in the current manuscript was available online, thus the Signed Informed Consent Form(s) or Document(s) was not applied for the current manuscript.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: The data underlying this article are available in individual referenced papers, the Finngen database (https://r7.finngen.fi/) and the IEU OpenGWAS project (https://gwas.mrcieu.ac.uk/).
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yu Bai, MD, PhD, Academic Research, Associate Professor, Researcher, Department of Gastroenterology, Changhai Hospital, No. 168 Changhai Road, Yangpu District, Shanghai 200433, China. changhaibaiyu@smmu.edu.cn
Received: December 9, 2023
Peer-review started: December 9, 2023
First decision: December 14, 2023
Revised: January 1, 2024
Accepted: January 23, 2024
Article in press: January 23, 2024
Published online: February 16, 2024
Processing time: 53 Days and 2.4 Hours
Abstract
BACKGROUND

Previous studies have indicated bidirectional associations between urate levels and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD). However, it remains unclear whether the observations are causal because of confounding factors.

AIM

To investigate the causal associations between urate levels and IBD using bidirectional Mendelian randomization (MR).

METHODS

Independent genetic variants for urate levels and IBD were selected as instrumental variables from published genome-wide association studies (GWASs). Summary statistics for instrument-outcome associations were retrieved from three separate databases for IBD (the UK Biobank, the FinnGen database and a large GWAS meta-analysis) and one for urate levels (a large GWAS meta-analysis). MR analyses included the inverse-variance-weighted method, weighted-median estimator, MR-Egger and sensitivity analyses (MR-PRESSO). A meta-analysis was also conducted to merge the data from separate outcome databases using a fixed-effects model.

RESULTS

Genetically higher serum urate levels were strongly associated with an increased risk of UC [odds ratio (OR): 1.95, 95% confidence interval (CI): 1.86-2.05] after outlier correction, and the ORs (95%CIs) for IBD and CD were 0.94 (95%CI: 0.86-1.03) and 0.91 (95%CI: 0.80-1.04), respectively. Animal studies have confirmed the positive association between urate levels and UC. Moreover, genetically predicted IBD was inversely related to urate levels (OR: 0.97, 95%CI: 0.94-0.99). However, no association was observed between genetically influenced UC or CD and urate levels.

CONCLUSION

Urate levels might be risk factors for UC, whereas genetically predicted IBD was inversely associated with urate levels. These findings provide essential new insight for treating and preventing IBD.

Keywords: Inflammatory bowel disease; Urate levels; Antioxidant; Mendelian randomization; Single nucleotide polymorphism

Core Tip: Previous observational studies have indicated the association between urate levels and inflammatory bowel disease (IBD) (including ulcerative colitis (UC) and Crohn’s disease). To overcome the limitations of conventional observational studies and investigate the causal association between urate levels and IBD, we conducted a bidirectional Mendelian randomization (MR) study. MR analysis revealed that higher urate levels may be risk factors for UC, and genetically predicted IBD was inversely associated with urate levels.