ABSTRACT: PURPOSE:Multiple sclerosis (MS) is a major demyelinating disease of the central nervous system with a strong genetic component. Previous studies have reported that the association of EVI5 rs11808092, CD58 rs2300747, and CIITA rs3087456 polymorphisms with the susceptibility to MS. However, the results were inconsistent. Thus, we conducted this meta-analysis to provide a more accurate estimation of the association between any of these polymorphisms and MS risk. METHODS:The PubMed, Embase, Chinese National Knowledge Infrastructure, Wan Fang databases and MSGene were used to search all potentially relevant studies. The odds ratio (OR) with 95% confidence interval (CI) was used to investigate the associations between these three polymorphisms and MS risk. RESULTS:16 independent case-control studies from 12 publications were finally included into this meta-analysis. The results showed that EVI5 rs11808092 polymorphism was related with increasing the development of MS under five genetic models (allelic: OR = 1.17, 95% CI = 1.10-1.24, P < 0.01; homozygous: OR = 1.37, 95% CI = 1.18-1.59, P < 0.01; heterozygous: OR = 1.16, 95% CI = 1.07-1.26, P < 0.01; recessive: OR = 1.28, 95% CI = 1.11-1.48, P < 0.01; and dominant: OR = 1.19, 95% CI = 1.11-1.48, P < 0.01). CD58 rs2300747 polymorphism was found to be associated with decreasing MS risk in three genetic models (allelic: OR = 0.86, 95% CI = 0.78-0.94, P < 0.01; heterozygous: OR = 0.85, 95% CI = 0.76-0.94, P < 0.01, and dominant: OR = 0.84, 95% CI = 0.76-0.93, P < 0.01). However, this meta-analysis indicated that CIITA rs3087456 polymorphism was not related to multiple sclerosis. CONCLUSIONS:The mutant alleles of EVI5 rs11808092 polymorphism may increase the susceptibility to MS while those of CD58 rs2300747 polymorphism may decrease MS risk. In addition, CIITA rs3087456 polymorphism might not be associated with MS.