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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Systems Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1437999
This article is part of the Research Topic Genetics and multi-omics approach in metabolic liver disorders View all articles

Genetically predicted serum ferritin mediates the association between Inflammatory Cytokines and Non-alcoholic fatty liver disease

Provisionally accepted
Xiaoqian Liu Xiaoqian Liu 1JianHong Jin JianHong Jin 1*Baofa Wang Baofa Wang 1*Linpu Ge Linpu Ge 2*
  • 1 Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China
  • 2 Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China

The final, formatted version of the article will be published soon.

    Objective: Investigating the causal relationship between inflammatory cytokines and Non-al coholic fatty liver disease(NAFLD) and identifying and quantifying the role of serum ferrit in as a potential mediator.Methods: Genetic summary statistics were derived from open genome-wide association study (GWAS) databases. We conducted a two-sample Mendelian randomization (MR) analysis to investigate the relationship between inflammatory cytokines (8,293 individuals ) and NAFLD (8,434 cases, 770,180 controls). Furthermore, we used two-step MR to quantitate the proportion of the effect of serum ferritin-mediated inflammatory cytokines on NAFLD. In this study, we primarily utilized inverse-variance-weighted Mendelian randomization (MR-IVW) and reverse MR analysis methods, while other methods were also performed for sensitivity analysis ， false discovery rate (FDR) <0.0012 as statistical significance in MR analyses.Our results indicated that high levels of Eotaxin, regulated upon activation norma l T cell expressed and presumably secreted(RANTES), Interleukin-2(IL-2), macrophage mig ration inhibitory factor(MIF), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Stem cell factor(SCF) were associated with increased risks of NAFLD, while high C utaneous T cell-attracting chemokine(CTACK) and Interleukin-16(IL-16) levels that reduced the risk of NAFLD.The proportion of genetically predicted NAFLD mediated by ferritin was 2.1%(95% CI = 1.39%-5.61%).In conclusion, our study identified a causal relationship between inflammatory cytokines and NAFLD, with a small proportion of the effect mediated by ferritin, but a majority of the effect of inflammatory cytokines on NAFLD remains unclear. Further resea rch is needed on additional risk factors as potential mediators.

    Keywords: inflammatory cytokines, Non-alcoholic fatty liver disease, ferritin, Metabolism, Mendelian randomization

    Received: 24 May 2024; Accepted: 17 Oct 2024.

    Copyright: © 2024 Liu, Jin, Wang and Ge. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    JianHong Jin, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China
    Baofa Wang, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China
    Linpu Ge, Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang Province, China

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