Background: Under the hypothesis that the G-308A polymorphism in the promoter region of the tumor necrosis factor alpha gene might increase tumor necrosis factor alpha 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 17,030 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.