Department of Interventional Radiology, the First College of Clinical Medical Science, China Three Gorges University, Yichang, 443003, Hubei Province, China.
Department of Interventional Radiology, Yichang Central People's Hospital, Yichang, 443003, Hubei Province, China.
Sci Rep. 2024 Nov 21;14(1):28884. doi: 10.1038/s41598-024-80483-2.
Liver cirrhosis, a common liver disease, currently lacks specific targeted therapies. This study investigates the potential therapeutic effects of serum circulating proteins on cirrhosis from a genetic perspective, and identified six associated plasma proteins (SERPINA1, PSG5, NCAN, APOE, ADH1B, GM2A). To search for therapeutic drugs associated with circulating proteins, databases such as DrugBank and DGIdb are utilized. Phenome-wide Mendelian Randomization analysis of the six significantly associated proteins revealed that GM2A exhibited no notable side effects as a therapeutic target for cirrhosis, SERPINA1 may offer additional therapeutic benefits for cholelithiasis and emphysema. ADH1B serves as a potential drug target that could simultaneously reduce the risk of alcohol-related disorders and hypertension. Furthermore, PSG5 and APOE might increase the risk of cardiovascular and neurological diseases, and NCAN has the potential to additionally reduce the risk of developing non-alcoholic fatty liver disease NAFLD. In conclusions, this study substantiates, from a genetic perspective, the potential therapeutic target role of six plasma proteins in cirrhosis, while comprehensively evaluating their side effects.
肝硬化是一种常见的肝脏疾病，目前缺乏特异性的靶向治疗方法。本研究从遗传角度探讨了血清循环蛋白对肝硬化的潜在治疗作用，并鉴定出与肝硬化相关的六种血浆蛋白（SERPINA1、PSG5、NCAN、APOE、ADH1B、GM2A）。为了寻找与循环蛋白相关的治疗药物，我们利用了 DrugBank 和 DGIdb 等数据库。对这六种显著相关蛋白进行全基因组孟德尔随机化分析表明，GM2A 作为肝硬化的治疗靶点，没有明显的副作用；SERPINA1 可能为胆石症和肺气肿提供额外的治疗益处；ADH1B 可能成为一种潜在的药物靶点，同时降低与酒精相关的疾病和高血压的风险。此外，PSG5 和 APOE 可能增加心血管和神经系统疾病的风险，而 NCAN 有可能进一步降低非酒精性脂肪性肝病（NAFLD）的发病风险。综上所述，本研究从遗传角度证实了六种血浆蛋白在肝硬化中的潜在治疗靶点作用，并全面评估了它们的副作用。
