Impact of Mitochondrial-Associated Proteins on Erectile Dysfunction: Insights From Mendelian Randomization Analysis

IF 2 4区 医学 Q3 ANDROLOGY
Andrologia Pub Date : 2025-07-22 DOI:10.1155/and/4615891
Yijia Fu, Xin Zhang, Jie Wang, Runnan Xu, Qi Zhang, Jianxiong Ma, Bodong Lv
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Abstract

Background: Mitochondrial dysfunction is implicated in the pathogenesis of erectile dysfunction (ED); establishing a causal relationship remains a challenge. This study employed a two-sample Mendelian randomization (MR) approach to investigate the potential causal associations between mitochondria-associated proteins and ED.

Methods: Association data on mitochondria-associated proteins from the IEU OpenGWAS database were used for exposure, whereas ED association data from the UK Biobank and FinnGen databases served as the outcome. MR analyses were conducted separately, primarily employing the inverse-variance weighted (IVW) method and supplemented by the MR-Egger, weighted median, simple mode, and weighted mode methods. Sensitivity analyses included Cochran’s Q test, MR-Egger test, leave-one-out analysis, and MR-PRESSO. A meta-analysis of both databases was conducted to enhance the credibility of the results.

Results: Meta-analysis revealed a significant causal relationship between five mitochondria-related proteins and ED: 39S ribosomal protein L33 (RPL33; p = 0.013; odds ratio [OR] = 0.94; 95% confidence interval [CI]: 0.90–0.99), mitochondrial ubiquitin ligase activator of NFKB-1 (MULAN1; p = 0.039; OR = 1.08; 95% CI: 1.00–1.16), nucleoside diphosphate-linked moiety X motif -8 (NUDT8; p = 0.035; OR = 0.92; 95% CI: 0.84–0.99), pyruvate dehydrogenase (acetyl-transferring) kinase isozyme-1 (PDK1; p = 0.047; OR = 1.07; 95% CI: 1.00–1.14), and serine-tRNA ligase (SerRS; p = 0.005; OR = 1.18; 95% CI: 1.05–1.33). Sensitivity analyses revealed no abnormalities.

Conclusion: RPL33 and NUDT8 exhibited potential protective effects against ED, whereas MULAN1, PDK1, and SerRS may increase the risk of developing ED. These findings offer new insights into the role of mitochondrial dysfunction in ED pathogenesis and may guide the development of future therapeutic strategies.

Abstract Image

线粒体相关蛋白对勃起功能障碍的影响:孟德尔随机化分析的见解
背景:线粒体功能障碍与勃起功能障碍(ED)的发病机制有关;建立因果关系仍然是一个挑战。本研究采用双样本孟德尔随机化(MR)方法来研究线粒体相关蛋白与ED之间的潜在因果关系。方法:暴露使用IEU OpenGWAS数据库中线粒体相关蛋白的关联数据,而ED关联数据来自UK Biobank和FinnGen数据库。MR分析分别进行,主要采用反方差加权(IVW)方法,辅以MR- egger、加权中位数、简单模态和加权模态方法。敏感性分析包括科克伦Q检验、艾格先生检验、遗漏分析和MR-PRESSO。对两个数据库进行了荟萃分析,以提高结果的可信度。结果:荟萃分析显示,5种线粒体相关蛋白与ED之间存在显著的因果关系:39S核糖体蛋白L33 (RPL33;P = 0.013;优势比[OR] = 0.94;95%可信区间[CI]: 0.90-0.99),线粒体泛素连接酶激活物NFKB-1 (MULAN1;P = 0.039;or = 1.08;95% CI: 1.00-1.16),核苷二磷酸连接片段X基序-8 (NUDT8;P = 0.035;or = 0.92;95% CI: 0.84-0.99),丙酮酸脱氢酶(乙酰转移)激酶同工酶-1 (PDK1;P = 0.047;or = 1.07;95% CI: 1.00-1.14),丝氨酸- trna连接酶(SerRS;P = 0.005;or = 1.18;95% ci: 1.05-1.33)。敏感性分析未发现异常。结论:RPL33和NUDT8对ED具有潜在的保护作用,而MULAN1、PDK1和SerRS可能会增加ED发生的风险。这些发现为线粒体功能障碍在ED发病机制中的作用提供了新的见解,并可能指导未来治疗策略的发展。
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来源期刊
Andrologia
Andrologia 医学-男科学
CiteScore
5.60
自引率
8.30%
发文量
292
审稿时长
6 months
期刊介绍: Andrologia provides an international forum for original papers on the current clinical, morphological, biochemical, and experimental status of organic male infertility and sexual disorders in men. The articles inform on the whole process of advances in andrology (including the aging male), from fundamental research to therapeutic developments worldwide. First published in 1969 and the first international journal of andrology, it is a well established journal in this expanding area of reproductive medicine.
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