Qiu Zeming, Cheng Long, Wang Qinyuan, Dong Zhilong
Department of Urology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, Gansu, China.
The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, Gansu, China.
Sex Med. 2025 Jan 9;12(6):qfae091. doi: 10.1093/sexmed/qfae091. eCollection 2024 Dec.
Currently, the treatment and prevention of erectile dysfunction (ED) remain highly challenging.
This study conducted a systematic druggable genome-wide Mendelian randomization (MR) analysis to identify potential therapeutic targets for ED.
A proteome-wide MR approach was employed to investigate the causal effects of plasma proteins on ED. Subsequently, summary data-based MR (SMR) analysis was performed to identify potential drug targets for ED. Enrichment analysis and protein-protein interaction (PPI) networks revealed the functional characteristics and biological relevance of these potential therapeutic targets. Drug prediction and molecular docking studies were conducted to validate the pharmacological activity of these identified targets. Finally, a systematic MR analysis was conducted to assess upstream intervention factors, such as lifestyles and diseases, associated with these targets, providing insights for the prevention and treatment of ED.
This study identified several potential therapeutic targets for ED.
Proteome-wide MR analysis revealed that 126 genetically predicted plasma proteins were causally associated with ED. SMR analysis indicated that TMEM9 was associated with an increased risk of ED, while MDH1, NQO1, QDPR, ARL4D, TAGLN2, and PPP1R14A were associated with a decreased risk of ED. These potential targets were primarily enriched in metabolic and redox-related biological processes. Molecular docking indicated that the predicted drugs had favorable binding affinities with the proteins, further confirming the pharmacological value of these targets. Finally, 6 plasma proteins (MDH1, NQO1, QDPR, ARL4D, TAGLN2, and TMEM9) could be modulated by lifestyle- and disease-related factors.
This study provides new insights into the etiology and potential drug targets of ED and contributes to the development of more effective treatments for ED and reducing the cost of drug development.
This is a systematic and extensive study exploring the causal relationship between plasma proteins and ED, which helps to provide a comprehensive perspective to understand the role of potential targets in ED. However, we did not conduct this study in different types of ED or different stages of ED progression.
In summary, this study identified 7 plasma proteins causally associated with ED and provided new insights into the etiology and potential drug targets for ED.
目前，勃起功能障碍（ED）的治疗和预防仍然极具挑战性。
本研究进行了一项全基因组可成药孟德尔随机化（MR）分析，以确定ED的潜在治疗靶点。
采用全蛋白质组MR方法研究血浆蛋白对ED的因果效应。随后，进行基于汇总数据的MR（SMR）分析，以确定ED的潜在药物靶点。富集分析和蛋白质-蛋白质相互作用（PPI）网络揭示了这些潜在治疗靶点的功能特征和生物学相关性。进行药物预测和分子对接研究，以验证这些已确定靶点的药理活性。最后，进行系统的MR分析，以评估与这些靶点相关的上游干预因素，如生活方式和疾病，为ED的预防和治疗提供见解。
本研究确定了几个ED的潜在治疗靶点。
全蛋白质组MR分析显示，126种基因预测的血浆蛋白与ED存在因果关系。SMR分析表明，跨膜蛋白9（TMEM9）与ED风险增加相关，而苹果酸脱氢酶1（MDH1）、醌氧化还原酶1（NQO1）、喹啉酸磷酸核糖转移酶（QDPR）、ADP核糖基化因子4D（ARL4D）、转谷氨酰胺酶2（TAGLN2）和蛋白磷酸酶1调节亚基14A（PPP1R14A）与ED风险降低相关。这些潜在靶点主要富集在代谢和氧化还原相关的生物学过程中。分子对接表明，预测的药物与蛋白质具有良好的结合亲和力，进一步证实了这些靶点的药理价值。最后，6种血浆蛋白（MDH1、NQO1、QDPR、ARL4D、TAGLN2和TMEM9）可受生活方式和疾病相关因素的调节。
本研究为ED的病因和潜在药物靶点提供了新的见解，有助于开发更有效的ED治疗方法并降低药物开发成本。
这是一项系统且广泛的研究，探索了血浆蛋白与ED之间的因果关系，有助于从全面的角度理解潜在靶点在ED中的作用。然而，我们未在不同类型的ED或ED进展的不同阶段进行这项研究。
总之，本研究确定了7种与ED存在因果关系的血浆蛋白，并为ED的病因和潜在药物靶点提供了新的见解。
