Interleukin-17 and inflammatory bowel disease: a 2-sample Mendelian randomization study

Yangke Cai; Xuan Jia; Liyi Xu; Hanwen Chen; Siyuan Xie; Jianting Cai

doi:10.3389/fimmu.2023.1238457

Interleukin-17 and inflammatory bowel disease: a 2-sample Mendelian randomization study

Front Immunol. 2023 Nov 17:14:1238457. doi: 10.3389/fimmu.2023.1238457. eCollection 2023.

Authors

Yangke Cai^#^{1

2}, Xuan Jia^#¹, Liyi Xu¹, Hanwen Chen¹, Siyuan Xie^{1

2}, Jianting Cai¹

Affiliations

¹ Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
² Zhejiang University Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

^# Contributed equally.

Abstract

Introduction: Observational studies have discovered a contradictory phenomenon between interleukin-17 (IL-17) and inflammatory bowel disease (IBD). The study aimed to confirm the causal association between each subtype of IL-17 and IBD.

Methods: We performed a 2-sample univariable and multivariable mendelian randomization (MR) to determine which subtype of IL-17 is causally related to IBD and its subtypes, and used a series of sensitivity analysis to examine the reliability of the main MR assumptions.

Results: We found that IL-17B, IL-17E and IL-17RB were significantly associated with an increased risk of UC (IL-17B: OR: 1.26, 95% CI, 1.09-1.46, P < 0.01; IL-17E: OR: 1.17, 95% CI, 1.05-1.30, P < 0.01; IL-17RB: OR: 1.30, 95% CI, 1.20-1.40, P < 0.0001) while IL-17C and IL-17RC showed causal effects on the increased risk of CD (IL-17C: OR: 1.23, 95% CI, 1.21-1.26, P < 0.0001; IL-17RC: OR: 2.01, 95% CI, 1.07-3.75, P=0.03). The results of multivariable MR (MVMR) showed that the causal effects of IL-17B and IL-17E on UC were unilaterally dependent on IL-17RB, while the effects of IL-17C and IL-17RC on CD were interdependent.

Discussion: Our study provided new genetic evidence for the causal relationships between each subtype of IL-17 and IBD, promoting future mechanistic research in IBD.

Keywords: Mendelian randomization; genetic epidemiology; inflammatory bowel disease; interleukin-17; multivariable Mendelian randomization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Inflammatory Bowel Diseases* / genetics
Interleukin-17* / genetics
Mendelian Randomization Analysis
Reproducibility of Results

Substances

Interleukin-17
IL17A protein, human

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the National Natural Science Foundation of China (No. 82073160);