Effects of Blood Pressure and Antihypertensive Drugs on Rheumatoid Arthritis: A Mendelian Randomization, Network Pharmacology, and Experimental Validation

作者：Fulin Yan, Weishan Wu, Mengxiong Luo, Sidian Yang, Jiguang Yin, Xiangpeng Wang · 发表于：International Journal of General Medicine · 年份：2026 · DOI：10.2147/ijgm.s575696 · 研究领域：Rheumatoid Arthritis Research and Therapies、Genetic Associations and Epidemiology、Osteoarthritis Treatment and Mechanisms

Background: We conducted a Mendelian randomization study in conjunction with a network pharmacology study to provide an analytical elucidation of the potential causal relationship between blood pressure and antihypertensive drugs and rheumatoid arthritis. Methods: First, a Mendelian randomization analysis was performed using large-scale GWAS data to assess the causal associations of systolic/diastolic blood pressure and 12 antihypertensive drug classes with rheumatoid arthritis. The analytical model of inverse variance weighting was primarily utilized. Second, we constructed a "drug-component-target-disease" regulatory network graph and analyzed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment. Third, we validated some of the mined data through molecular docking technology using BIOVIA Discovery Studio 2019. Finally, animal experiments were performed to verify. Results: The results indicated that elevated diastolic blood pressure was significantly associated with an increased risk of rheumatoid arthritis. Among antihypertensive drugs, adrenergic neuron blockers, central antihypertensives, and potassium-sparing diuretics/aldosterone antagonists reduced the risk of rheumatoid arthritis. Sensitivity analyses demonstrated the absence of pleiotropy or heterogeneity. In addition, after network pharmacology research, the molecular docking of its active ingredients with their targets was carried out, and the link potential was relatively ideal. Construction of a r...