-308 G > A of TNF-α gene promoter decreases the risk of multiple sclerosis: A meta-analysis

Background: Environmental and genetic factors are thought to be involved in the pathogenesis of multiple sclerosis (MS). Polymorphisms of tumor necrosis factor (TNF)-alpha -308 were implicated in MS risk in several case-control association studies. However, the studies have shown inconsistent results. Objectives: To address the association of G/A polymorphisms of TNF-alpha -308 with MS risk by meta-analysis. Methods: Thirteen studies were included. Pooled odds ratios (ORs) together with 95% confidence intervals (CIs) were calculated. Results: A total of 1870 cases and 2769 controls were included in the meta-analysis. The pooled result indicated that -308 A allele is significantly associated with reduced risk of MS compared with -308 G allele (A vs. G, p = 0.022). The same pattern of the result was also obtained in the contrasts of AA+GA vs. GG (p = 0.008) and GA vs. GG (p = 0.007). For AA vs. GG or AA vs. GA+GG, no significant association was detected most likely caused by very low frequency or non-availability of homozygote genotype AA for all of the studies. Conclusions: TNF-alpha -308 A allele is associated with reduced risk of MS.