{"title":"线粒体蛋白与动脉瘤和主动脉夹层风险的因果关系:一项孟德尔随机研究。","authors":"Lei Wang, Yuzuo Lin, Ziyan Lin, Qingtong Wu, Guodong Zhong, Liangwan Chen","doi":"10.1186/s13019-025-03389-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>This study identified potential genetic associations between mitochondrial proteins and AA/AD. Targeting these mitochondrial proteins may help prevent the occurrence of AA/AD.</p>","PeriodicalId":15201,"journal":{"name":"Journal of Cardiothoracic Surgery","volume":"20 1","pages":"181"},"PeriodicalIF":1.5000,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971758/pdf/","citationCount":"0","resultStr":"{\"title\":\"Causal relationship between mitochondrial proteins and risks of aortic aneurysms and aortic dissection: a Mendelian randomization study.\",\"authors\":\"Lei Wang, Yuzuo Lin, Ziyan Lin, Qingtong Wu, Guodong Zhong, Liangwan Chen\",\"doi\":\"10.1186/s13019-025-03389-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>This study identified potential genetic associations between mitochondrial proteins and AA/AD. Targeting these mitochondrial proteins may help prevent the occurrence of AA/AD.</p>\",\"PeriodicalId\":15201,\"journal\":{\"name\":\"Journal of Cardiothoracic Surgery\",\"volume\":\"20 1\",\"pages\":\"181\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2025-04-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971758/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Cardiothoracic Surgery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13019-025-03389-8\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cardiothoracic Surgery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13019-025-03389-8","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Causal relationship between mitochondrial proteins and risks of aortic aneurysms and aortic dissection: a Mendelian randomization study.
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.
期刊介绍:
Journal of Cardiothoracic Surgery is an open access journal that encompasses all aspects of research in the field of Cardiology, and Cardiothoracic and Vascular Surgery. The journal publishes original scientific research documenting clinical and experimental advances in cardiac, vascular and thoracic surgery, and related fields.
Topics of interest include surgical techniques, survival rates, surgical complications and their outcomes; along with basic sciences, pediatric conditions, transplantations and clinical trials.
Journal of Cardiothoracic Surgery is of interest to cardiothoracic and vascular surgeons, cardiothoracic anaesthesiologists, cardiologists, chest physicians, and allied health professionals.