Causal relationship between mitochondrial proteins and risks of aortic aneurysms and aortic dissection: a Mendelian randomization study
Abstract Background Mitochondrial dysfunction may be linked to the development of aortic aneurysm (AA) and aortic dissection (AD). This study aimed to evaluate the potential associations between proteins related to mitochondrial function and the risks of AA/AD using Mendelian randomization (MR). Met...
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BMC
2025-04-01
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| Series: | Journal of Cardiothoracic Surgery |
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| Online Access: | https://doi.org/10.1186/s13019-025-03389-8 |
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| author | Lei Wang Yuzuo Lin Ziyan Lin Qingtong Wu Guodong Zhong Liangwan Chen |
| author_facet | Lei Wang Yuzuo Lin Ziyan Lin Qingtong Wu Guodong Zhong Liangwan Chen |
| author_sort | Lei Wang |
| collection | DOAJ |
| description | Abstract Background Mitochondrial dysfunction may be linked to the development of aortic aneurysm (AA) and aortic dissection (AD). This study aimed to evaluate the potential associations between proteins related to mitochondrial function and the risks of AA/AD using Mendelian randomization (MR). Methods Large-scale publicly available genome-wide association studies (GWAS) and FinnGen summary data were utilized for MR analysis. The causal relationship between mitochondrial proteins and AA/AD was assessed using inverse-variance weighted (IVW) as the primary method. Sensitivity analyses were conducted to detect heterogeneity and pleiotropy by Cochran’s Q test, MR-Egger test, MR-PRESSO global test, and “leave-one-out” analysis. Results There were potential causal relationships between several mitochondrial proteins and AA/AD. Specifically, the iron-sulfur cluster assembly enzyme ISCU (OR = 1.165, 95% CI: 1.051–1.291, P = 0.004) and NFU1 iron-sulfur cluster scaffold homolog (OR = 1.184, 95% CI: 1.056–1.329, P = 0.004) were identified as potential risk factors for AA; whereas the 39 S ribosomal protein L14 (OR = 0.868, 95% CI: 0.764–0.987, P = 0.031) was found to be a protective factor for AA. Furthermore, 39 S ribosomal protein L33 (OR = 1.134, 95% CI: 1.010–1.274, P = 0.033) and cytochrome C oxidase subunit 5B (OR = 1.330, 95% CI: 1.037–1.706, P = 0.025) were associated with increased risks of AD; whereas the 39 S ribosomal protein L52 (OR = 0.736, 95% CI: 0.550–0.984, P = 0.038) and mitochondrial ubiquitin ligase activator of NFKB 1 (OR = 0.806, 95% CI: 0.656–0.989, P = 0.039) were identified as potential protective factors for AD. Sensitivity analysis confirmed the stability of the results. Conclusions This study identified potential genetic associations between mitochondrial proteins and AA/AD. Targeting these mitochondrial proteins may help prevent the occurrence of AA/AD. |
| format | Article |
| id | doaj-art-61a81e561f4047748dcb0f92de957195 |
| institution | DOAJ |
| issn | 1749-8090 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
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| series | Journal of Cardiothoracic Surgery |
| spelling | doaj-art-61a81e561f4047748dcb0f92de9571952025-08-20T03:04:53ZengBMCJournal of Cardiothoracic Surgery1749-80902025-04-0120111110.1186/s13019-025-03389-8Causal relationship between mitochondrial proteins and risks of aortic aneurysms and aortic dissection: a Mendelian randomization studyLei Wang0Yuzuo Lin1Ziyan Lin2Qingtong Wu3Guodong Zhong4Liangwan Chen5Department of Cardiovascular Surgery, Fujian Medical University Union HospitalUnion College of Clinical Medicine, Fujian Medical University Union HospitalUnion College of Clinical Medicine, Fujian Medical University Union HospitalUnion College of Clinical Medicine, Fujian Medical University Union HospitalDepartment of Pathology, Fujian Province Second People’s Hospital, The Second Affiliated Hospital of Fujian University of Traditional Chinese MedicineDepartment of Cardiovascular Surgery, Fujian Medical University Union HospitalAbstract Background Mitochondrial dysfunction may be linked to the development of aortic aneurysm (AA) and aortic dissection (AD). This study aimed to evaluate the potential associations between proteins related to mitochondrial function and the risks of AA/AD using Mendelian randomization (MR). Methods Large-scale publicly available genome-wide association studies (GWAS) and FinnGen summary data were utilized for MR analysis. The causal relationship between mitochondrial proteins and AA/AD was assessed using inverse-variance weighted (IVW) as the primary method. Sensitivity analyses were conducted to detect heterogeneity and pleiotropy by Cochran’s Q test, MR-Egger test, MR-PRESSO global test, and “leave-one-out” analysis. Results There were potential causal relationships between several mitochondrial proteins and AA/AD. Specifically, the iron-sulfur cluster assembly enzyme ISCU (OR = 1.165, 95% CI: 1.051–1.291, P = 0.004) and NFU1 iron-sulfur cluster scaffold homolog (OR = 1.184, 95% CI: 1.056–1.329, P = 0.004) were identified as potential risk factors for AA; whereas the 39 S ribosomal protein L14 (OR = 0.868, 95% CI: 0.764–0.987, P = 0.031) was found to be a protective factor for AA. Furthermore, 39 S ribosomal protein L33 (OR = 1.134, 95% CI: 1.010–1.274, P = 0.033) and cytochrome C oxidase subunit 5B (OR = 1.330, 95% CI: 1.037–1.706, P = 0.025) were associated with increased risks of AD; whereas the 39 S ribosomal protein L52 (OR = 0.736, 95% CI: 0.550–0.984, P = 0.038) and mitochondrial ubiquitin ligase activator of NFKB 1 (OR = 0.806, 95% CI: 0.656–0.989, P = 0.039) were identified as potential protective factors for AD. Sensitivity analysis confirmed the stability of the results. Conclusions This study identified potential genetic associations between mitochondrial proteins and AA/AD. Targeting these mitochondrial proteins may help prevent the occurrence of AA/AD.https://doi.org/10.1186/s13019-025-03389-8MitochondriaAortic aneurysmAortic dissectionMendelian randomization |
| spellingShingle | Lei Wang Yuzuo Lin Ziyan Lin Qingtong Wu Guodong Zhong Liangwan Chen Causal relationship between mitochondrial proteins and risks of aortic aneurysms and aortic dissection: a Mendelian randomization study Journal of Cardiothoracic Surgery Mitochondria Aortic aneurysm Aortic dissection Mendelian randomization |
| title | Causal relationship between mitochondrial proteins and risks of aortic aneurysms and aortic dissection: a Mendelian randomization study |
| title_full | Causal relationship between mitochondrial proteins and risks of aortic aneurysms and aortic dissection: a Mendelian randomization study |
| title_fullStr | Causal relationship between mitochondrial proteins and risks of aortic aneurysms and aortic dissection: a Mendelian randomization study |
| title_full_unstemmed | Causal relationship between mitochondrial proteins and risks of aortic aneurysms and aortic dissection: a Mendelian randomization study |
| title_short | Causal relationship between mitochondrial proteins and risks of aortic aneurysms and aortic dissection: a Mendelian randomization study |
| title_sort | causal relationship between mitochondrial proteins and risks of aortic aneurysms and aortic dissection a mendelian randomization study |
| topic | Mitochondria Aortic aneurysm Aortic dissection Mendelian randomization |
| url | https://doi.org/10.1186/s13019-025-03389-8 |
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