association between tumor necrosis factor- α-308 g/a polymorphism and multiple sclerosis: a systematic review and meta-analysis

multiple sclerosis (ms) is a complex polygenic disease in which gene-environment interactions are important. a number of studies have investigated the association between tumor necrosis factor-α (tnf-α) -308 g/a polymorphism (substitution g→a, designated as tnf1 and tnf2) and ms susceptibility in different populations, but the results of individual studies have been inconsistent. therefore, performing a systematic review and meta-analysis of the published studies is desirable. we sought to quantitatively summarize the association between tnf-α-308 g/a polymorphism and ms. the medline and scopus databases were searched to identify potentially relevant case-control studies published in english journals up to january 2010. a meta-analysis of these studies was performed. summary odds ratios (ors) and 95% confidence intervals (cis) were calculated under fixed and random effects models. twenty-one eligible studies, comprising 2880 patients with ms and 3579 controls, were included in the meta-analysis. the overall pooled ors (95%ci) for tnf2 versus tnf1 and tnf2 carriers (2/2+2/1) versus non-carriers (1/1) were 1.02 (0.86-1.21) and 0.99 (0.8-1.24), respectively. in the european populations, the pooled ors (95%ci) for tnf 2/1 versus 1/1 were 0.85 (0.73-0.98), which was statistically significant. however, the other results did not support this finding. the pooled ors (95%ci) for tnf 2/1 versus 1/1 and tnf 2/2 versus 2/1 were not statistically significant in the overall population. in addition, the pooled ors for tnf2/2 versus tnf2/1+1/1 and tnf2/2 versus tnf1/1 were not statistically significant. our meta-analysis does not support the role of tnf-α -308 g/a polymorphism in developing ms.