Serum urate is associated with an increased risk of inflammatory bowel disease: A bidirectional Mendelian randomization study  

作　　者：Song Zhang Xue Fang Le Kang Xiang-Yu Sui Miao Liu Yu-Jia Luo Shuo Fu Zhao-Shen Li Sheng-BingZhao Yu Bai 

机构地区：[1]Department of Gastroenterology,Changhai Hospital,Shanghai 200433,China [2]Department of Gastroenterology,Changhai Hospital,Second Military Medical University/Naval Medical University,Shanghai 200433,China [3]Digestive Endoscopy Center,Changhai Hospital,Naval/Second Military Medical University,Shanghai 200433,China [4]National Clinical Research Center for Digestive Diseases,Shanghai 200433,China

出　　处：《World Journal of Clinical Cases》2024年第5期891-902,共12页世界临床病例杂志

基　　金：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.

摘　　要：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 bidirec-tional Mendelian randomization(MR).METHODS Independent genetic variants for urate levels and IBD were selected as instru-mental 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.

关 键 词：Inflammatory bowel disease Urate levels ANTIOXIDANT Mendelian randomization Single nucleotide polymorphism 

分 类 号：R574[医药卫生—消化系统]