title: Cytotoxic T-lymphocyte associated antigen-4 gene polymorphisms and primary biliary cirrhosis: a systematic review.
abstract: OBJECTIVE
  The cytotoxic T-lymphocyte antigen 4 (CTLA4) is an inhibitory receptor expressed on activated and regulatory T lymphocytes. Polymorphisms could have remarkable effects on susceptibility to autoimmunity. However, the associations between CTLA-4 polymorphisms and primary biliary cirrhosis (PBC) remain ambiguous. The aim of this meta-analysis is to determine more precise estimations of the relationship.
  
  
  METHODS
  From literature retrieval from PubMed, Web of Science, Science Direct, and the Chinese National Knowledge Infrastructure (CNKI) Database, the publications on the associations between rs231775, rs3087243, rs5742909, rs231725 and rs11571317 polymorphisms of CTLA4 and PBC through June 2011 were collected. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated in fixed or random model, I(2) was calculated to examine heterogeneity, and funnel plots were plotted to examine small study effects with Revman 5.1 and Stata 11.
  
  
  RESULTS
  Overall, a significantly increased risk was found for G versus A allele for rs231775 (OR = 1.28, 95% CI = 1.17-1.41). For rs3087243, a significant association was found for AA versus GG genotype (OR = 0.66; 95% CI = 0.55-0.80). When subgroup analysis by ethnicity was performed, the same association was only found in Caucasians. For rs231725, the OR values (95% CI) for GG versus AA, GA versus AA and G versus A allele were 0.52 (0.40-0.68), 0.74 (0.60-0.92) and 0.73 (0.61-0.88). No significant associations were found for other polymorphisms.
  
  
  CONCLUSIONS
  The G allele of rs231775 is a risk factor for PBC, while AA genotype of rs3087243 and GG, GA and G allele of rs231725 show negative associations with PBC.
authors.affiliation: Department of Epidemiology, School of Public Health, Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Zheng
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Zhang
authors.forename: Dian-Wu
authors.initials: DW
authors.lastname: Liu
mesh_terms: D060908:CTLA-4 Antigen / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human