| الملخص: | Ce Shuai,* Szeman Cheung,* Li Zhang, Han Cao, Yongyong Yuan, Qinyi Ge, Youcong Wang, Xia Li, Jie Zheng, Feng Xue Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng Xue, Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Email xuefeng204108@126.com Jie Zheng, Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Email jie-zheng2001@126.comBackground: Epidemiological studies have revealed a close association between psoriasis and non-alcoholic fatty liver disease (NAFLD), but the causal relationship and underlying mechanisms remain unclear.Materials and Methods: In this study, we used genome-wide association study (GWAS) data from the MRC Integrative Epidemiology Unit (MRC-IEU) to investigate the causal relationship between psoriasis and NAFLD, as well as potential mediators. Two-sample and two-step MR analyses were conducted, followed by bulk and single-cell transcriptomic analyses to validate our MR findings. In vivo validation was performed using Enzyme-Linked Immunosorbent Assay (Sample of patients (n=10)), immunohistochemistry, and liver bulk transcriptomic analysis.Results: The two-sample MR analysis revealed that genetically predicted psoriasis significantly increased the risk of NAFLD (OR = 1.07, 95% CI = 1.03– 1.12, p = 0.001). Mediation analysis suggested that psoriasis was associated with elevated plasma Interleukin-1 receptor antagonist protein (IL-1RA) levels (OR = 1.02, 95% CI = 1.00– 1.05, p = 0.031), which in turn raised the risk of NAFLD (OR = 1.15, 95% CI = 1.04– 1.27, p = 0.006). In vivo experiments demonstrated elevated IL-1RA levels in the skin and plasma of psoriasis patients. Similarly, imiquimod (IMQ)-induced psoriasis mouse models exhibited increased IL-1RA levels in plasma and liver, accompanied by liver inflammation. MR and colocalization analysis indicated a positive correlation between IL-1RA, apolipoprotein B, and cholesterol.Conclusion: Our study demonstrates that genetically predicted psoriasis increases the risk of NAFLD, and plasma IL-1RA may serve as a potential mediator between psoriasis and NAFLD.Keywords: psoriasis, non-alcoholic fatty liver disease, mendelian randomization, imiquimod-induced mouse model
|
|---|
