Association between tumor necrosis factor- alpha-308 G/A polymorphism and multiple sclerosis: a systematic review and meta-analysis

ABSTRACT

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-alpha [TNF-alpha] -308 G/A polymorphism [substitution G[rightwards arrow]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-alpha-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-alpha -308 G/A polymorphism in developing MS