Objective The aim of this meta-analysis was to undertake a meta-analysis to evaluate the correlation between cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) gene rs221775 A>G single nucleotide polymorphism and the susceptibility of multiple sclerosis (MS) susceptibility. spinal cord are damaged. And it was reported that MS is the most common diagnosized autoimmune NVP-BEP800 disease which can affect the central nervous system. Clinical epidemology study estimated that about 2,300,000 subjects were affected by MS globally in the year of 2013, and about 20,000 people died from MS at the same year [1]. MS has the ability to reduce the communication of the central nervous system, which can lead to a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems [2]. Generally, MS is not believed to be a hereditary disease, but some studies indicated that the genetic variations could have an association with the increasing risk of developing MS [3]. One of the related genes is cytotoxic T lymphocyte-associated antigen 4(CTLA-4), which is expressed on the surface of T cells and is critical in inhibiting T cell activation. Several studies have reported a significant correlation between CTLA-4 gene rs221775A>G single nucleotide polymorphism and multiple sclerosis susceptibility [4, 5]. However, other studies have not find a significant correlation [6-8]. Thus, we performed a meta-analysis by pooling all the available data related to CTLA-4 gene rs221775A>G single nucleotide polymorphism and multiple sclerosis susceptibility in order to further evaluted the corrlation. 2.?Method 2.1. Publication search strategy The open published studies about the CTLA-4 gene rs221775A>G single nucleotide polymorphism and multiple sclerosis susceptibility were searched in the databases of Pubmed Embase and China National Knowledge Infrastructure (CNKI). The case-control or cohort studies published in English or Chinese were all searched in the databases before Jan 2016. The search strategy and text words were: cytotoxic T lymphocyte associated antigen/CTLA-4/CTLA4, multiple sclerosis/MS or polymorphism. The references for the included papers were also screened to MTRF1 identify additional potential suitable studies which were not indexed in the pubmed or CNKI databases. 2.2. Inclusion and exclusion criteria The inclusion criteria were as follows: (1) the study design was cases-cotrol or cohort; (2) the paper was published in English or Chinese; (3) the genotyping method is correct; (4) the frequency of AA, AG and GG nucleotide NVP-BEP800 can NVP-BEP800 be extracted from the original study. And the exclusion criteria were: (1) the study design type were review or case report; (2) studies with duplicate published datas; (3) Studies publised in other languages (not English or Chinese); (4) the data extracted from the original studies was not enough to calculate the ORs. 2.3. Data evaluation Two reviewers (XIAO Haibing & CAO Xu) of this manuscript independently reviewed the papers and extracted the data according to the Cochrane Handbook. The general information such as first author, the paper publication year, the country of the study performed, and the race of the included subjects for each of the included paper were extacted. The frequency of AA, AG and GG nucleotide for the include 20 studies were canrefully extracted and corss checked, which was used to calculated the pooled ORs. If disagreements were encountered, the discussion was made and a third reviewer was consulted. 2.4. Statistical analysis Stata/SE 11.0StataCorp LP, http://www.stata.com were used for statistical analysis. The correlation between CTLA-4 gene rs221775A>G single nucleotide polymorphism and multiple sclerosis susceptibility was demonstrated by odds ratio (OR) and its 95% confidence interval (95%CI). Statistical heterogeneity among studies was evaluated by I2 [9]. If significant heterogeneity was found (I250%), the random-effect method (Dersimonian-Laird method) was used to pool the data. Inversely, fixed-effect method was applied. The publication bias was detected by Beggs funnelplot. 3.?Results 3.1. General information of the included studies Through searching the databases, 86.