title: CTLA-4 +49 G/A Polymorphism Confers Autoimmune Disease Risk: An Updated Meta-Analysis.
abstract: BACKGROUND
  Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a pivotal role in immune homeostasis. Dysregulated expression of CTLA-4 leads to many autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes (T1D). There has been a controversial association between the CTLA-4 +49 G/A SNP (rs231775) and autoimmune diseases. Therefore, this meta-analysis was performed to assess the link between rs231775 and autoimmune disease risk.
  
  
  METHODS
  We retrieved the available studies from PUBMED and EMBASE through February, 2016 and then performed meta-analyses that included all populations, as well as by ethnicity.
  
  
  RESULTS
  After evaluating data from 4732 patients and 6270 healthy controls that included both Caucasian and Asian ethnicities, we found that rs231775 is strongly associated with autoimmune disease incidence in a homozygote comparison (GG vs. AA, 95% confidence interval [95% CI] 1.382-2.401), in a heterozygote comparison (AG vs. AA, 95% CI 1.151-1.611), in an allelic model (T allele vs. G allele, 95% CI 1.109-1.441), in a dominant model (GG/AG vs. AA, 95% CI 1.220-1.787), and in a recessive model (GG vs. AA/AG, 95% CI 1.128-1.661). The OR (odds ratio) from all models suggested a very significant association between rs231775 and autoimmune diseases.
  
  
  CONCLUSIONS
  Our present study indicates that CTLA-4 +49 G/A (rs231775) is associated with the susceptibility of autoimmune disease. Hence, rs231775 might be utilized as a diagnostic biomarker in both Asian and Caucasian populations.
authors.affiliation: Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Department of Liver Surgery, First Affiliated Hospital of Nanjing Medical University , Nanjing, P.R. China .
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Department of Liver Surgery, First Affiliated Hospital of Nanjing Medical University , Nanjing, P.R. China .
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Department of Liver Surgery, First Affiliated Hospital of Nanjing Medical University , Nanjing, P.R. China .
authors.forename: Yunjie
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Department of Liver Surgery, First Affiliated Hospital of Nanjing Medical University , Nanjing, P.R. China .
authors.forename: Hao
authors.initials: H
authors.lastname: Lu
authors.affiliation: Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Department of Liver Surgery, First Affiliated Hospital of Nanjing Medical University , Nanjing, P.R. China .
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Department of Liver Surgery, First Affiliated Hospital of Nanjing Medical University , Nanjing, P.R. China .
authors.forename: Xuehao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Department of Liver Surgery, First Affiliated Hospital of Nanjing Medical University , Nanjing, P.R. China .
authors.forename: Ye
authors.initials: Y
authors.lastname: Fan
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics; D044466:Asian People / Q000235:genetics; D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human
keywords: CTLA-4 +49 G/A; autoimmune disease; meta; polymorphism; rs231775