Objective:Accumulated studies have explored gene polymorphisms and circulating levels of tumor necrosis factor (TNF)-alpha and insulin-like growth factor (IGF)-1 in the etiology of ischemic stroke (IS). Of the numerous etiopathological factors for IS, a single-nucleotide polymorphism (SNP) rs1800629 located in the TNF-alpha gene promoter region and increased levels of TNF-alpha were found to be associated with IS in different ethnic backgrounds. However, the published results are inconsistent and inconclusive. The primary objective of this meta-analysis was to investigate the concordance between rs1800629 polymorphism and IS. A secondary aim was to explore circulating levels of TNF-alpha and IGF-1 with IS in different ethnic backgrounds and different sourced specimens. Methods: In this study, we examined whether rs1800629 genetic variant and levels of TNF-alpha and IGF-1 were related to the etiology of IS by performing a meta-analysis. Relevant case-control studies were retrieved by database searching and systematically selected according to established inclusion criteria. Results:A total of 47 articles were identified that explored the relationship between the rs1800629 polymorphism and levels of TNF-alpha and IGF-1 with IS risk susceptibility. Statistical analyses revealed a significant association between the rs1800629 polymorphism and levels of TNF-alpha and IGF-1 with IS pathogenesis. Conclusion:Our findings demonstrated that the TNF-alpha rs1800629 polymorphism, the increased levels of TNF-alpha, and decreased levels of IGF-1 were involved in the etiology of IS.