Identification of novel drug targets for liver cirrhosis and its potential side-effects by human plasma proteome

Abstract 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, A...

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Main Authors: Qing-Ao Xiao, Wen-Jiang Zhao, Jing Yu, Lei Qin, Xiao-Lin Zhang, Jin Yu
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-024-80483-2
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author Qing-Ao Xiao
Wen-Jiang Zhao
Jing Yu
Lei Qin
Xiao-Lin Zhang
Jin Yu
author_facet Qing-Ao Xiao
Wen-Jiang Zhao
Jing Yu
Lei Qin
Xiao-Lin Zhang
Jin Yu
author_sort Qing-Ao Xiao
collection DOAJ
description Abstract 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.
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spelling doaj-art-952e95045e574a63b0cd16b2ea3d723f2025-08-20T02:22:21ZengNature PortfolioScientific Reports2045-23222024-11-0114111110.1038/s41598-024-80483-2Identification of novel drug targets for liver cirrhosis and its potential side-effects by human plasma proteomeQing-Ao Xiao0Wen-Jiang Zhao1Jing Yu2Lei Qin3Xiao-Lin Zhang4Jin Yu5Department of Interventional Radiology, the First College of Clinical Medical Science, China Three Gorges UniversityDepartment of Interventional Radiology, the First College of Clinical Medical Science, China Three Gorges UniversityDepartment of Interventional Radiology, the First College of Clinical Medical Science, China Three Gorges UniversityDepartment of Interventional Radiology, the First College of Clinical Medical Science, China Three Gorges UniversityDepartment of Interventional Radiology, the First College of Clinical Medical Science, China Three Gorges UniversityDepartment of Interventional Radiology, the First College of Clinical Medical Science, China Three Gorges UniversityAbstract 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.https://doi.org/10.1038/s41598-024-80483-2Durg targetsMendelian randomizationProteome-wide mendelian randomizationCirrhosis
spellingShingle Qing-Ao Xiao
Wen-Jiang Zhao
Jing Yu
Lei Qin
Xiao-Lin Zhang
Jin Yu
Identification of novel drug targets for liver cirrhosis and its potential side-effects by human plasma proteome
Scientific Reports
Durg targets
Mendelian randomization
Proteome-wide mendelian randomization
Cirrhosis
title Identification of novel drug targets for liver cirrhosis and its potential side-effects by human plasma proteome
title_full Identification of novel drug targets for liver cirrhosis and its potential side-effects by human plasma proteome
title_fullStr Identification of novel drug targets for liver cirrhosis and its potential side-effects by human plasma proteome
title_full_unstemmed Identification of novel drug targets for liver cirrhosis and its potential side-effects by human plasma proteome
title_short Identification of novel drug targets for liver cirrhosis and its potential side-effects by human plasma proteome
title_sort identification of novel drug targets for liver cirrhosis and its potential side effects by human plasma proteome
topic Durg targets
Mendelian randomization
Proteome-wide mendelian randomization
Cirrhosis
url https://doi.org/10.1038/s41598-024-80483-2
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