Investigating the Association and Causality Between Hyperuricemia and Peripheral Atherosclerosis: A Study Based on Mendelian Randomization and Bioinformatics Analysis
DOI:
https://doi.org/10.71321/4w6y6229Keywords:
Hyperuricemia, Atherosclerosis, Mendelian randomization, Bioinformatics, Hub targets, Immune infiltrationAbstract
Objective: To investigate the genetic causal association and shared molecular mechanisms between hyperuricemia (HUA) and peripheral atherosclerosis using Mendelian randomization (MR) and bioinformatics approaches, providing a theoretical basis for early disease screening and intervention.
Methods: An MR strategy was employed. Based on Genome-Wide Association Study (GWAS) datasets, the causal relationship between HUA and peripheral atherosclerosis was assessed through instrumental variable selection, multi-model MR analysis (including Inverse-Variance Weighted, IVW), and sensitivity analysis validation. Simultaneously, relevant datasets from the GEO database were utilized to identify differentially expressed genes (DEGs) common to both diseases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed, and a Protein-Protein Interaction (PPI) network was constructed to identify hub genes. Immune infiltration characteristics were analyzed using CIBERSORT.
Results: A significant positive causal association was found between hyperuricemia and atherosclerosis (OR=1.296, 95% CI: 1.112-1.512, P=0.0009). Bioinformatics analysis identified 133 intersecting DEGs, which were enriched in immune-inflammatory-related functions and pathways. Hub genes screened from the PPI network included IL1B, CD86, and CSF1R. Immune infiltration analysis revealed characteristic remodeling of the immune microenvironment in both groups.
Conclusion: A significant positive genetic causal association exists between HUA and peripheral atherosclerosis. The shared pathogenic mechanisms may involve the aforementioned hub genes, activation of immune-inflammatory pathways, and abnormal immune infiltration. The findings provide a theoretical framework and potential experimental targets for early risk prediction and targeted intervention in HUA complicated with peripheral atherosclerosis.
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