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。

IF 1.5 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS
Lei Wang, Yuzuo Lin, Ziyan Lin, Qingtong Wu, Guodong Zhong, Liangwan Chen
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引用次数: 0

摘要

背景:线粒体功能障碍可能与主动脉瘤(AA)和主动脉夹层(AD)的发生有关。本研究旨在利用孟德尔随机化(Mendelian randomization, MR)评估线粒体功能相关蛋白与AA/AD风险之间的潜在关联。方法:利用大规模公开的全基因组关联研究(GWAS)和FinnGen汇总数据进行MR分析。采用逆方差加权(IVW)作为主要方法评估线粒体蛋白与AA/AD的因果关系。采用Cochran’s Q检验、MR-Egger检验、MR-PRESSO全局检验和“留一”分析进行敏感性分析,检测异质性和多效性。结果:几种线粒体蛋白与AA/AD存在潜在的因果关系。其中,铁硫簇组装酶ISCU (OR = 1.165, 95% CI: 1.051 ~ 1.291, P = 0.004)和NFU1铁硫簇支架同源物(OR = 1.184, 95% CI: 1.056 ~ 1.329, P = 0.004)被确定为AA的潜在危险因素;39 S核糖体蛋白L14 (OR = 0.868, 95% CI: 0.764 ~ 0.987, P = 0.031)是AA的保护因子。此外,39s核糖体蛋白L33 (OR = 1.134, 95% CI: 1.010-1.274, P = 0.033)和细胞色素C氧化酶亚基5B (OR = 1.330, 95% CI: 1.037-1.706, P = 0.025)与AD风险增加相关;39 S核糖体蛋白L52 (OR = 0.736, 95% CI: 0.550-0.984, P = 0.038)和线粒体泛素连接酶激活因子NFKB 1 (OR = 0.806, 95% CI: 0.656-0.989, P = 0.039)被确定为AD的潜在保护因子。敏感性分析证实了结果的稳定性。结论:本研究确定了线粒体蛋白与AA/AD之间潜在的遗传关联。靶向这些线粒体蛋白可能有助于预防AA/AD的发生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
Journal of Cardiothoracic Surgery
Journal of Cardiothoracic Surgery 医学-心血管系统
CiteScore
2.50
自引率
6.20%
发文量
286
审稿时长
4-8 weeks
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.
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