Exploring the impact of inflammatory cytokines on alcoholic liver disease: a Mendelian randomization study with bioinformatics insights into potential biological mechanisms.
Zhitao Chen, Chenchen Ding, Kailei Chen, Chicheng Lu, Qiyong Li
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引用次数: 0
Abstract
Background: Alcoholic liver disease (ALD) significantly contributes to global morbidity and mortality. The role of inflammatory cytokines in alcohol-induced liver injury is pivotal yet not fully elucidated.Objectives: To establish a causal link between inflammatory cytokines and ALD using a Mendelian Randomization (MR) framework.Methods: This MR study utilized genome-wide significant variants as instrumental variables (IVs) for assessing the relationship between inflammatory cytokines and ALD risk, focusing on individuals of European descent. The approach was supported by comprehensive sensitivity analyses and augmented by bioinformatics tools including differential gene expression, protein-protein interactions (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and analysis of immune cell infiltration.Results: Our findings reveal that increased levels of stem cell growth factor beta (SCGF-β, beta = 0.141, p = .032) and interleukin-7 (IL-7, beta = 0.311, p = .002) are associated with heightened ALD risk, whereas higher levels of macrophage inflammatory protein-1α (MIP-1α, beta = -0.396, p = .004) and basic fibroblast growth factor (bFGF, beta = -0.628, p = .008) are linked to reduced risk. The sensitivity analyses support these robust causal relationships. Bioinformatics analyses around inflammatory cytokine-associated SNP loci suggest multiple pathways through which cytokines influence ALD.Conclusion: The genetic evidence from this study convincingly demonstrates that certain inflammatory cytokines play directional roles in ALD pathogenesis. These findings provide insights into the complex biological pathways involved and underscore the potential for developing targeted therapies that modulate these inflammatory responses, ultimately improving clinical outcomes for ALD patients.
期刊介绍:
The American Journal of Drug and Alcohol Abuse (AJDAA) is an international journal published six times per year and provides an important and stimulating venue for the exchange of ideas between the researchers working in diverse areas, including public policy, epidemiology, neurobiology, and the treatment of addictive disorders. AJDAA includes a wide range of translational research, covering preclinical and clinical aspects of the field. AJDAA covers these topics with focused data presentations and authoritative reviews of timely developments in our field. Manuscripts exploring addictions other than substance use disorders are encouraged. Reviews and Perspectives of emerging fields are given priority consideration.
Areas of particular interest include: public health policy; novel research methodologies; human and animal pharmacology; human translational studies, including neuroimaging; pharmacological and behavioral treatments; new modalities of care; molecular and family genetic studies; medicinal use of substances traditionally considered substances of abuse.