Warfarin use and vestibular dysfunction insights from NHANES data, network pharmacology, Mendelian randomization, and molecular docking

Abstract

Abstract Despite numerous anticoagulants available, warfarin is widely used due to its efficacy and cost-effectiveness in treating thromboembolic diseases. However, its potential impact on vestibular function remains unexplored. This study investigates the association between warfarin use and vestibular dysfunction using data from the NHANES database and examines underlying mechanisms through network pharmacology, Mendelian randomization (MR), and molecular docking. We conducted a cross-sectional analysis of NHANES data (1999–2004) to evaluate the prevalence of vestibular dysfunction among warfarin users. Network pharmacology identified overlapping genes between warfarin targets and vestibular dysfunction-related genes. MR analysis assessed the causal relationship, and molecular docking examined interactions between warfarin and significant genes. The study included 1681 participants, revealing a higher prevalence of vestibular dysfunction in warfarin users. Multiple regression analysis confirmed a significant association between warfarin use and vestibular dysfunction. Network pharmacology identified 31 overlapping genes, with MAPK8 emerging as a key gene through MR analysis. Molecular docking showed a strong binding affinity between warfarin and MAPK8. Findings suggest that warfarin use is significantly associated with vestibular dysfunction, potentially through interactions with MAPK8. This highlights the importance of monitoring vestibular function in patients on warfarin therapy and considering genetic factors to personalize treatment. Future research should explore these mechanisms further and validate findings in broader populations.

Keywords

• Warfarin
• Vestibular dysfunction
• Network Pharmacology
• Mendelian randomization
• MAPK8