Prognostic Associations and Functional Implications of Angiogenesis-Related miRNA Variants in Ischemic Stroke

Ischemic stroke is a multifactorial cerebrovascular disease that remains a leading cause of long-term disability and mortality worldwide. Despite advances in acute treatment, recurrence rates remain high, and nearly half of survivors experience persistent neurological deficits. Therefore, identifying genetic biomarkers that contribute to early diagnosis, risk prediction, and therapeutic improvement is increasingly important. MicroRNAs, small non-coding RNAs involved in gene regulation, have been recognized for their critical roles in vascular development and angiogenesis. This study investigated the association between angiogenesis-related miRNA gene polymorphisms and ischemic stroke risk using a population-based case–control design. Genotyping and statistical analysis revealed that miR-21 rs13137 A > T and miR-126 rs4636297 G > A were significantly associated with stroke susceptibility. The TT genotype of miR-21 rs13137 demonstrated a protective effect (p = 0.019); the AA genotype of miR-126 rs4636297 was associated with increased risk (p = 0.006), along with its dominant model (p = 0.007). Additionally, deep learning models were utilized to evaluate gene–gene and gene–environment interactions, enhancing predictive accuracy and identifying synergistic effects between miRNA polymorphisms and clinical risk factors. In summary, specific miRNA variants may serve as novel biomarkers for ischemic stroke, providing valuable insight into genetic susceptibility and supporting the advancement of precision medicine strategies.