فهرست نشریات علمی دسترسی آزاد ایران

Background and Objectives: Previous studies have highlighted the anti-diabetic drugs as repurposing candidates for Atrial fibrillation (AF), but the disease-modifying effects are still unclear. In this study, the drug-target Mendelian randomization (MR) analysis was utilized to investigate the relationship between various anti-diabetic drugs and AF.   Methods: Using a study design involving MR, we scrutinized the association between various anti-diabetic medications and the risk of AF. Genetic summary information for diabetes and AF was acquired from UK Biobank (UKBB), Finngen, and several independent genome-wide association studies (GWASs). Rigorous replication validation procedures were meticulously carried out to ensure the robustness of our findings. Moreover, detailed information on drug targets was collected from the “Chembl” database.   Results: The Thiazolidinediones drug called "Rosiglitazone" and the Amino Acid drug called "Tyrosine" have been found to be associated with a significantly higher risk of AF. This heightened risk is attributed to the activation of specific proteins: Rosiglitazone activates CRHBP (Corticotropin Releasing Hormone Binding Protein), while Tyrosine activates MPO (Myeloperoxidase) and CA1 (Carbonic Anhydrase 1). Importantly, these protein activations were linked to a notably higher incidence of AF, a finding that was consistently confirmed in external validation datasets. No pleiotropy or genetic confounding was detected in the sensitivity studies.   Conclusion: The genetic variation in the targets of "Rosiglitazone" and "Tyrosine" is associated with a higher likelihood of developing AF. This groundbreaking discovery is expected to significantly contribute to the progress of correlational research on early clinical prevention and the core mechanism of AF medication therapy.