Shi Shiya, Zhou Yanjie, Zhang He, Zhu Yalan, Jiang Pengjun, Xie Chengxia, Feng Tianyu, Zeng Yuping, He He, Luo Yao, Chen Jie
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Biomedicines. 2024 Oct 4;12(10):2264. doi: 10.3390/biomedicines12102264.
Observational studies have highlighted the pivotal role of inflammatory cytokines in cirrhosis progression. However, the existence of a causal link between inflammatory cytokines and cirrhosis remains uncertain. In this study, we conducted a bidirectional Mendelian randomization (MR) analysis at a summarized level to illuminate the potential causal relationship between the two variables.
This study utilized genetic variance in cirrhosis and inflammatory cytokines from a genome-wide association study (GWAS) of European descent. The MR-PRESSO outlier test, Cochran's Q test, and MR-Egger regression were applied to assess outliers, heterogeneity, and pleiotropy. The inverse variance weighted method and multiple sensitivity analyses were used to evaluate causalities. Furthermore, the validation set was used for simultaneous data validation.
The inflammatory cytokine monocyte chemoattractant protein 3 (MCP-3) was supposedly associated with a greater risk of cirrhosis. And cirrhosis was significantly correlated with increased levels of hepatocyte growth factor (HGF).
This study suggests that MCP-3 might be associated with the etiology of cirrhosis, while several inflammatory cytokines could potentially play a role in its downstream development. Additionally, the progression of cirrhosis was associated with elevated levels of HGF, suggesting a possible role for liver repair functions.
观察性研究强调了炎性细胞因子在肝硬化进展中的关键作用。然而，炎性细胞因子与肝硬化之间因果关系的存在仍不确定。在本研究中，我们在汇总水平上进行了双向孟德尔随机化（MR）分析，以阐明这两个变量之间的潜在因果关系。
本研究利用了来自欧洲血统全基因组关联研究（GWAS）中肝硬化和炎性细胞因子的遗传变异。应用MR-PRESSO异常值检验、 Cochr an's Q检验和MR-Egger回归来评估异常值、异质性和多效性。采用逆方差加权法和多种敏感性分析来评估因果关系。此外，验证集用于同步数据验证。
炎性细胞因子单核细胞趋化蛋白3（MCP-3）可能与更高的肝硬化风险相关。并且肝硬化与肝细胞生长因子（HGF）水平升高显著相关。
本研究表明，MCP-3可能与肝硬化的病因有关，而几种炎性细胞因子可能在其下游发展中发挥作用。此外，肝硬化的进展与HGF水平升高有关，提示肝脏修复功能可能发挥作用。
