Single Nucleotide Polymorphisms in Stroke: Evidence Across Susceptibility, Prognosis, and Recurrence; A Systematic Review.

Stroke is a leading cause of global morbidity and mortality. Genetic variation, particularly single nucleotide polymorphisms (SNPs), has been implicated not only in stroke susceptibility but also in post-stroke outcomes and recurrence. However, evidence remains fragmented across populations, stroke subtypes, and clinical endpoints. We conducted a systematic review in accordance with PRISMA guidelines, searching PubMed, Scopus, Web of Science, Embase, Cochrane Library, and Google Scholar through January 2025. Eligible studies included case–control, cohort, genome-wide association, and Mendelian randomization studies examining associations between SNPs and incident stroke risk, post-stroke outcomes, or recurrence. Data were extracted on study design, population, genetic variants, and effect estimates. Study quality was assessed using the Newcastle–Ottawa Scale, supplemented by qualitative consideration of genetic-study–specific biases. Twenty-seven studies were included, encompassing diverse populations and stroke-related outcomes. SNPs in genes related to inflammation (e.g., TNF-α, HMGB1), lipid metabolism (ANGPTL4, DIAPH1), oxidative stress (MTHFR), and regulatory RNAs (MIAT, microRNAs) were associated with stroke susceptibility, subtype-specific risk, post-stroke recovery, or recurrence. Associations varied substantially by study design, population, and outcome, with most findings derived from candidate-gene studies and limited independent replication. Genetic variants across multiple biological pathways are associated with stroke-related phenotypes, including susceptibility, prognosis, and recurrence. However, heterogeneity of outcomes and study designs limits causal inference and clinical translation. Larger multi-ethnic studies with replication and functional validation are required before SNP-based risk stratification can be routinely applied.