Liu Shihan, Zhang Lingli, Luo Wenlong
Department of Otorhinolaryngology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Otorhinolaryngology, Central Hospital Affiliated to Chongqing University of Technology, Chongqing, China.
Sci Rep. 2025 Apr 6;15(1):11748. doi: 10.1038/s41598-025-96681-5.
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.
尽管有多种抗凝剂可供使用，但华法林因其在治疗血栓栓塞性疾病方面的疗效和成本效益而被广泛应用。然而，其对前庭功能的潜在影响仍未得到探索。本研究利用美国国家健康与营养检查调查（NHANES）数据库的数据，调查华法林使用与前庭功能障碍之间的关联，并通过网络药理学、孟德尔随机化（MR）和分子对接研究潜在机制。我们对NHANES数据（1999 - 2004年）进行了横断面分析，以评估华法林使用者中前庭功能障碍的患病率。网络药理学确定了华法林靶点与前庭功能障碍相关基因之间的重叠基因。MR分析评估了因果关系，分子对接研究了华法林与重要基因之间的相互作用。该研究纳入了1681名参与者，结果显示华法林使用者中前庭功能障碍的患病率更高。多元回归分析证实了华法林使用与前庭功能障碍之间存在显著关联。网络药理学确定了31个重叠基因，通过MR分析发现丝裂原活化蛋白激酶8（MAPK8）是关键基因。分子对接显示华法林与MAPK8之间具有很强的结合亲和力。研究结果表明，华法林的使用与前庭功能障碍显著相关，可能是通过与MAPK8相互作用。这突出了对华法林治疗患者的前庭功能进行监测以及考虑遗传因素以实现个性化治疗的重要性。未来的研究应进一步探索这些机制，并在更广泛的人群中验证研究结果。
