Effect of the G-308A polymorphism of the tumor necrosis factor α gene on the risk of ischemic heart disease and ischemic stroke: A meta-analysis

Background Under the hypothesis that the G-308A polymorphism in the promoter region of the tumor necrosis factor α gene might increase tumor necrosis factor α expression, several investigations have been performed to examine the influence of the -308A allele on the risk of cardiovascular events. The results of these studies, however, have been conflicting. To provide a more robust estimate of the putative effect of the G-308A polymorphism on the risk of cerebrocardiovascular events, we did 2 meta-analyses that examined the role of the -308A variant in both ischemic heart disease (IHD) and ischemic stroke. Methods We applied both fixed- and random-effects models to combine odds ratios (OR) and 95% CIs, and publication bias and heterogeneity were explored. Results Data of 17030 subjects from 23 studies were used. Overall, in populations predominantly of European ancestry, no association between the G-308A polymorphism and IHD under a dominant model (AA + GA vs GG) was observed: OR, 1.07; 95% CI, 0.94-1.21; P = .32. Similarly, the -308A allele was not associated with ischemic stroke considering all studies: OR, 0.99; 95% CI, 0.70-1.41, P = .96. However, analysis by ancestry revealed that Asian subjects harboring the -308A variant were approximately 40% less likely to have stroke compared to the GG genotype: OR, 0.62; 95% CI, 0.44-0.86; P = .004. Conclusions These results suggest that the G-308A polymorphism is unlikely to be associated with the development of IHD, whereas it might be a protective factor for ischemic stroke in Asians only.