Bioinformatics Analysis Of A Functional Angpt1 Variant That Interferes With Mir-607 And Its Association With Susceptibility And Outcome Of Ischemic Stroke In A Han Population

Purpose: Ischemic stroke (IS) is a major cause of disability and death. We used bioinfor-matics approaches to investigate a functional ANGPT1 variant that interferes with miR-607 and explored its association with IS. Materials and Methods: An IS expression microarray (GSE16561) was downloaded from the GEO and used to identify differentially expressed genes (DEGs) and functional enrich-ment pathways. Analyses showed that ANGPT1 participated in six key pathways and was susceptible to a key functional polymorphism rs2507799. We genotyped 567 IS patients and 500 controls for ANGPT1 rs2507799. Luciferase assays were also conducted to investigate the binding between miR-607 and ANGPT1 rs2507799. Results: In total, we identified 458 DEGs between IS patients and healthy controls in the GSE16561 dataset. GO functional enrichment analysis showed that these DEGs were mainly enriched in cell-substrate junctions, the regulation of peptide secretion, and the regulation of cytokine secretion involved in immune response. ANGPT1 rs2507799 T-carriers had a significantly higher risk of IS (Dominant model: OR = 1.48, 95% CI = 1.01-2.17, P = 0.044). IS patients harboring the TC/TT genotype experienced significantly more severe injuries in terms of neurological function (Dominant model: OR = 2.06, 95% CI = 1.28-3.31, P = 0.003). Analysis also showed that IS patients harboring the TC/TT genotype had a significantly worse outcome (Dominant model: OR = 2.22, 95% CI = 1.35-3.67, P = 0.002). Luciferase assays indicated that miR-607 could affect luciferase activity by binding to the ANGPT1 mutant type. Conclusion: In this study, we used bioinformatical methods to investigate a key IS-related gene ANGPT1 and its functional polymorphism rs2507799. rs2507799 was found to be associated with a significantly increased risk for IS, a significantly more severe initial stroke severity, and a worse outcome. These results may help to improve the future management of ischemic stroke.