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

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.