title: Association between cytotoxic T lymphocyte antigen-4 polymorphism and type 1 diabetes: a meta-analysis.
abstract: Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is an important mediators of T-cell activation in autoimmune diseases. The association of polymorphisms of CTLA gene with type 1 diabetes (T1D) has widely been reported; however, the results are inconsistent. To obtain further insight into this topic, we performed a meta-analysis of 52 studies involving a total of 11,017 cases and 14,191 controls for 49A/G (rs231775) polymorphism of the CTLA-4 gene to evaluate the effect of CTLA-4 on genetic susceptibility for T1D. An overall random effects odds ratio of 1.41 (95% CI: 1.31-1.53, p<10(-5)) was found for G allele versus A allele. Significant results were also observed for heterozygous (OR=1.29, 95% CI: 1.16-1.45, p<10(-5)) and homozygous (OR=1.96, 95% CI: 1.66-2.31, p<10(-5)). When stratified by ethnicity, sample size, diagnostic criterion, HWE status, genotyping method, and onset types, significantly increased risks were found for the polymorphism in almost all genetic models. Subgroup analysis and meta-regression was used to identify potential source of heterogeneity. There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. This meta-analysis demonstrated that the G allele of rs231775 of CTLA-4 is a risk factor associated with increased T1D susceptibility.
authors.affiliation: Department of Orthopaedics Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China.
authors.forename: Zixian
authors.initials: Z
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Fei
authors.forename: Da
authors.initials: D
authors.lastname: Fu
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Yushui
authors.initials: Y
authors.lastname: Ma
authors.forename: Yichao
authors.initials: Y
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Xia
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
mesh_terms: D060908:CTLA-4 Antigen / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D012307:Risk Factors
chemical_list: D060908:CTLA-4 Antigen