AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025150093
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SHORT COMMUNICATION

Causal relationship between cathepsin H and type 1 diabetes: A Mendelian randomization study

Rui Jin Ran1 ,  Ao Wang2 ,  Ke Yi1,2*
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1 Department of Ophthalmology, Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases/Hubei Provincial Clinical Research Center for Nephrology, Minda Hospital of Hubei Minzu University, Hubei Minzu University, Enshi, Hubei, China
2 Key Laboratory of Obstetric and Gynecologic, and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
EJMO, 025150093 https://doi.org/10.36922/EJMO025150093
Received: 7 April 2025 | Revised: 12 May 2025 | Accepted: 22 May 2025 | Published online: 24 July 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Epidemiological studies investigating the relationship between cathepsins and diabetes mellitus (DM) have reported inconsistent results.

Objective: The objective of the study is to evaluate the potential causal relationship between cathepsins and DM using Mendelian randomization (MR) analysis.

Methods: A two-sample MR analysis was conducted using single nucleotide polymorphisms as instrumental variables to examine the effects of cathepsins on DM. Both univariable and multivariable MR analyses were employed to assess the individual and combined effects of cathepsins.

Results: Univariable MR analysis revealed a significant association between cathepsin H and an increased risk of type 1 DM using the inverse-variance weighted method (odds ratio = 1.104; 95% confidence interval = 1.065 – 1.145; p<0.001). Reverse MR analysis and sensitivity analysis supported the robustness of this finding. In the multivariable MR analysis, elevated cathepsin H levels were found to be significantly associated with an increased risk of type 1 DM (odds ratio = 1.090; 95% confidence interval = 1.048 – 1.133; p<0.001), even after adjusting for other cathepsin types. No significant associations were observed between cathepsins and the risk of type 2 DM or gestational DM.

Conclusion: The study highlights a significant causal relationship between cathepsin H and the risk of type 1 DM.

Keywords
Causal effect
Cathepsins
Diabetes mellitus
Mendelian randomization
Risk
Funding
This research was supported by the Open Project of Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases (Project Number: OIR202302Y) and Hubei Provincial Natural Science Foundation Joint Fund for Innovative Development (Project Number: 2024AFD070).
Conflict of interest
The authors declare that they have no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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