Causal association between matrix metalloproteinases and diabetic neuropathy: a two-sample Mendelian randomization study
ObjectiveDiabetic 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 resear...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2024.1429121/full |
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| author | Chao Bai Chao Bai Wenwen Yang Guangwei Qi Liuyu Yang Qingrui Wu Jieguang Peng Ning Wang Tao Liu |
| author_facet | Chao Bai Chao Bai Wenwen Yang Guangwei Qi Liuyu Yang Qingrui Wu Jieguang Peng Ning Wang Tao Liu |
| author_sort | Chao Bai |
| collection | DOAJ |
| description | ObjectiveDiabetic 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).MethodsData 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.ResultsIVW 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.ConclusionIn 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. |
| format | Article |
| id | doaj-art-7d717b9a5fd14120a44ae9427aa011b2 |
| institution | Kabale University |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj-art-7d717b9a5fd14120a44ae9427aa011b22025-01-14T04:11:03ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-01-011510.3389/fendo.2024.14291211429121Causal association between matrix metalloproteinases and diabetic neuropathy: a two-sample Mendelian randomization studyChao Bai0Chao Bai1Wenwen Yang2Guangwei Qi3Liuyu Yang4Qingrui Wu5Jieguang Peng6Ning Wang7Tao Liu8Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaPostdoctoral Research Station of Public Health and Preventive Medicine, Xinjiang Medical University, Urumqi, Xinjiang, ChinaDepartment of Clinical Nutrition, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaVascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaVascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaVascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaVascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaThe First Department of General Internal Medicine, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaSchool of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, ChinaObjectiveDiabetic 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).MethodsData 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.ResultsIVW 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.ConclusionIn 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.https://www.frontiersin.org/articles/10.3389/fendo.2024.1429121/fulldiabetic neuropathyMendelian randomizationMMP-2MMP-16GWAS |
| spellingShingle | Chao Bai Chao Bai Wenwen Yang Guangwei Qi Liuyu Yang Qingrui Wu Jieguang Peng Ning Wang Tao Liu Causal association between matrix metalloproteinases and diabetic neuropathy: a two-sample Mendelian randomization study Frontiers in Endocrinology diabetic neuropathy Mendelian randomization MMP-2 MMP-16 GWAS |
| title | Causal association between matrix metalloproteinases and diabetic neuropathy: a two-sample Mendelian randomization study |
| title_full | Causal association between matrix metalloproteinases and diabetic neuropathy: a two-sample Mendelian randomization study |
| title_fullStr | Causal association between matrix metalloproteinases and diabetic neuropathy: a two-sample Mendelian randomization study |
| title_full_unstemmed | Causal association between matrix metalloproteinases and diabetic neuropathy: a two-sample Mendelian randomization study |
| title_short | Causal association between matrix metalloproteinases and diabetic neuropathy: a two-sample Mendelian randomization study |
| title_sort | causal association between matrix metalloproteinases and diabetic neuropathy a two sample mendelian randomization study |
| topic | diabetic neuropathy Mendelian randomization MMP-2 MMP-16 GWAS |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2024.1429121/full |
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