Background/Aims To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets.
Methods We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options.
Results In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018–1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk of primary sclerosing cholangitis (PSC;1.193, 1.048– 1.357). On the other hand, CFHR1 (0.621, 0.497–0.776) and CFHR2 (0.824, 0.703–0.965) were inversely associated with the risk of alcohol-related cirrhosis. There were also significant inverse associations between C8 gamma chain (C8G) and PSC (0.832, 0.707–0.979), as well as the risk of metabolic dysfunction-associated steatotic liver disease (1.167, 1.036–1.314). Additionally, C1S (0.111, 0.018–0.672), C7 (1.631, 1.190–2.236), and CFHR2 (1.279, 1.059–1.546) were significantly associated with the risk of hepatocellular carcinoma. Proteins from the complement regulatory networks and various liver diseaserelated proteins share common biological processes. Furthermore, potential therapeutic drugs for various liver diseases were identified through drug repurposing based on the complement regulatory network.
Conclusions Our study suggests that certain complement components, including C1S, C1QC, CFHR1, CFHR2, CFHR5, C7, and C8G, might play a role in non-viral liver diseases and could be potential targets for drug development.
Citations
Citations to this article as recorded by
Untargeted Proteomics Profiling of Liver and Plasma in Fed and Fasted Liver‐Specific Glycogen Storage Disease Type Ia (GSD Ia) Mice: Toward Potential Protein Biomarkers Ruiqi Xiao, Hilda I. de Vries, Candelas Gross‐Valle, Aycha Bleeker, Terry G. J. Derks, Barbara M. Bakker, Maaike H. Oosterveer, Justina C. Wolters Journal of Inherited Metabolic Disease.2026;[Epub] CrossRef
КЛІНІКО-МОРФОЛОГІЧНІ АСПЕКТИ ПЕРВИННОГО НЕАЛКОГОЛЬНОГО СТЕАТОГЕПАТИТУ ЗА НАЯВНОСТІ КОМОРБІДНОЇ ПАТОЛОГІЇ ЖОВЧНОГО МІХУРА О. Ю. Фофанова, В. В. Феденько, З. Я. Гурик, Е. О. Кіндратів, І. Г. Лаб'як Art of Medicine.2025; : 113. CrossRef
Immune activation contributes recovery following pulmonary impairments by silica nanoparticles Caixia Guo, Xinying Zhao, Yan Li, Donglei Wang, Hailin Xu, Songqing Lv, Xueyan Li, Yanbo Li Journal of Hazardous Materials.2025; 496: 139403. CrossRef
Plasma complement proteins as biomarkers and therapeutic targets in chronic kidney disease: a Mendelian randomization analysis Yu-Peng Xu, Zheng-Qi Song, Ming-Li Chen, Yang-Li Fang, Hui-Di Zhang Renal Failure.2025;[Epub] CrossRef
Tissue-specific isoform usage and gene expression revealed through RNA-seq and ATAC-seq in developing cattle Sarem F. Khilji, Shangqian Xie, Gabrielle M. Becker, Katie A. Shira, Morgan R. Stegemiller, Julia L. Woods, Janet E. Williams, Lauren E. Christensen, Denise E. Konetchy, Darren E. Hagen,, Gordon K. Murdoch, Stephanie D. McKay, Brenda M. Murdoch BMC Genomics.2025;[Epub] CrossRef
Starting the journey: Understanding the roles of complement proteins in liver diseases through mendelian randomization Mohammad Saeid Rezaee-Zavareh, Naomy Kim, Ju Dong Yang Clinical and Molecular Hepatology.2024; 30(2): 150. CrossRef
Constructing a disulfidptosis-related prognostic signature of hepatocellular carcinoma based on single-cell sequencing and weighted co-expression network analysis Zelin Tian, Junbo Song, Jiang She, Weixiang He, Shanshan Guo, Bingchen Dong Apoptosis.2024; 29(9-10): 1632. CrossRef
Hepatocyte nuclear factor 4α is a critical factor for the production of complement components in the liver Carlos Ichiro Kasano-Camones, Satomi Yokota, Maiko Ohashi, Noriaki Sakamoto, Daichi Ito, Yoshifumi Saito, Ryo Uchida, Kazumi Ninomiya, Yusuke Inoue In Vitro Cellular & Developmental Biology - Animal.2024; 60(10): 1174. CrossRef
First
Prev
