Cytokine gene polymorphisms in multiple sclerosis: a meta-analysis of 45 studies including 7379 cases and 8131 controls.

Many environmental and genetic factors have been implicated in the development of multiple sclerosis. However, the aetiology has not been clarified yet. Therefore, using a meta-analytic approach, we tried to probe the potential association between various cytokine gene polymorphisms and the occurrence of multiple sclerosis. A comprehensive literature search yielded 45 eligible studies, which involved 7379 cases and 8131 controls. Totally, the effect of eight polymorphisms, i.e. IL-1A C[-889]T, IL-1B C[-511]T, IL-1B C[3953]T, IL-4 C[33]T, IL-10 C[-819]T, IL-10 G[-1082]A, tumour necrosis factor-a (TNFA) G[-308]A and TNFA G[-238]A, was evaluated in a random-effects meta-analysis. There was no evidence of statistically significant association between the aforementioned polymorphisms and multiple sclerosis. Publication bias and heterogeneity were absent in most analyses. Within its limitations, the current literature-based meta-analysis does not indicate that specific polymorphic variations of genes encoding pro-inflammatory and anti-inflammatory cytokines affect susceptibility to multiple sclerosis.