The Role of TNF-α 308G>A Polymorphism in the Risk for Ischemic Stroke

Background: Stroke is a common health problem; however, its pathogenesis is not clear. Several studies have examined the association of -308G>A promoter polymorphism in the tumor necrosis factor-alpha gene (TNF-alpha) with ischemic stroke susceptibility. However, the results of these studies are inconsistent and the sample sizes of most of the studies were small. Thus, a meta-analysis was conducted to provide a more robust estimate of the effect of the TNF-alpha 308G>A polymorphism on the risk for ischemic stroke. Methods: Odds ratios with 95% confidence intervals were used to assess the strength of the association of TNF-alpha polymorphisms with ischemic stroke. Cochran's Q statistic and the inconsistency index (I-2) were used to explore heterogeneity. Egger's test and inverted funnel plots were used to investigate publication bias. Results: Thirteen studies met the inclusion criteria involving 3515 cases and 3949 controls. A significant association was found between TNF-alpha 308G>A polymorphism and the development of ischemic stroke in the Asian population. However, no statistically significant association was observed in the overall analysis and in the Caucasian population. In the subgroup analysis by age, a significant association was found in the juvenile and adult populations, showing that TNF-alpha 308G>A polymorphism is associated with the risk for juvenile ischemic stroke. Conclusions: This study suggests that TNF-alpha 308G>A polymorphism is associated with the risk for juvenile ischemic stroke, whereas it is a protective factor for ischemic stroke in Asians and the adult population. However, in the overall analysis and in Caucasians, a significant association was not found.