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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Clinical Diabetes
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1429121

Causal Association Between Matrix Metalloproteinases and Diabetic Neuropathy: A Two-Sample Mendelian Randomization Study

Provisionally accepted
Chao Bai Chao Bai 1,2Wenwen Yang Wenwen Yang 1Guangwei Qi Guangwei Qi 1Liuyu Yang Liuyu Yang 1Qingrui Wu Qingrui Wu 1Jieguang Peng Jieguang Peng 1Ning Wang Ning Wang 1Tao Liu Tao Liu 3*
  • 1 First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uyghur Region, China
  • 2 Postdoctoral Research Station of Public Health and Preventive Medicine at Xinjiang Medical University, Xinjing, China
  • 3 School of Public Health, Xinjiang Medical University, Urumqi, China

The final, formatted version of the article will be published soon.

    Objective: Diabetic neuropathy (DN), a common and debilitating complication of diabetes, significantly impairs the quality of life of affected individuals. While multiple studies have indicated changes in the expression of specific matrix metalloproteinases (MMPs) in patients with DN, and basic research has reported the impact of MMPs on DN, there is a lack of systematic research and the causal relationship remains unclear. The objective of this research is to investigate the casual relationship between MMPs and DN through two-sample Mendelian randomization (MR). Methods: Data for this investigation were derived from genome-wide association studies (GWAS) of MMPs and DN. For the analysis using two-sample MR, methods such as inverse variance weighted (IVW), weighted median, weighted mode, and MR-Egger were utilized, with IVW serving as the primary measure for determining causative impacts. To evaluate the analysis' heterogeneity and potential pleiotropy, sensitivity examinations including MR-PRESSO analysis, Cochran's Q test, and the leave-one-out test were conducted. Results: IVW analysis revealed that genetically decreased serum MMP-2 level were causally associated with a high risk of DN (OR = 0.88, 95% CI: 0.79-0.99, P = 0.026). Genetically elevated serum MMP-16 level were causally associated with a high risk of DN (OR = 1.15, 95% CI: 1.01-1.32, P = 0.038). Genetic prediction results showed no causal association between other MMPs (MMP14/17/9/12/7/3) and DN. Sensitivity analyses showed no significant heterogeneity or pleiotropy. Conclusion: In summary, this research uncovered a genetic causal relationship between heightened MMP-16 levels and reduced MMP-2 concentrations, and DN risk. These discoveries offer new perspectives on the role of MMPs in DN etiology and establish a foundational premise for further investigations into MMP-targeted therapeutic interventions.

    Keywords: Diabetic neuropathy, Mendelian randomization, MMP-2, MMP-16, GWAS

    Received: 07 May 2024; Accepted: 26 Nov 2024.

    Copyright: © 2024 Bai, Yang, Qi, Yang, Wu, Peng, Wang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Tao Liu, School of Public Health, Xinjiang Medical University, Urumqi, China

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