Single‐Nucleotide Polymorphisms Associated With Aortic and Varicose Vein–Related Vascular Anomalies: A Systematic Review

Vascular anomalies, including aneurysms, dissections, varicose veins, and abnormal branching, arise from both genetic and environmental influences. While rare monogenic disorders underscore the genetic basis of vascular structure, common single‐nucleotide polymorphisms (SNPs) may also shape vascular morphology. SNPs collectively contribute to disease susceptibility and provide insight into pathways underlying vascular integrity. This systematic review, registered in PROSPERO (CRD42024519126) and conducted under PRISMA guidelines, searched PubMed, Embase, Web of Science, and Cochrane Library (February–May 2024; updated December 2024). Abstracts were screened in Rayyan by two reviewers, with study quality assessed using STREGA criteria and risk of bias using the Q‐Genie tool. Ninety‐five studies were included, reporting 697 SNPs. Most variants were intronic or regulatory, with 87 coding (12%). Associations were strongest for aortic disease and varicose veins. Effect sizes were generally modest, though rs1998049 ( β = 17.04, varicose veins) and rs1961177 ( β = 6.52, abdominal aortic aneurysm) showed stronger effects. Substantial interstudy heterogeneity in phenotype definitions, ancestry, and analytical approaches limited quantitative synthesis and asked for cautious interpretation of pooled findings. Gene Ontology analysis revealed enrichment of blood vessel morphogenesis, vasculogenesis, ventricular cardiac muscle tissue morphogenesis, and SMAD signaling ( q < 1.00 × 10 − 6). Evidence is most robust for aortic disease and varicose veins, while data on peripheral vasculature remain limited. Larger, ethnically diverse studies are needed to validate these associations and to clarify their biological and translational relevance.