title: CTLA-4 and MDR1 polymorphisms increase the risk for ulcerative colitis: A meta-analysis.
abstract: OBJECTIVE
  To evaluate the correlations between cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and multi-drug resistance 1 (MDR1) genes polymorphisms with ulcerative colitis (UC) risk.
  
  
  METHODS
  PubMed, EMBASE, Web of Science, Cochrane Library, CBM databases, Springerlink, Wiley, EBSCO, Ovid, Wanfang database, VIP database, China National Knowledge Infrastructure, and Weipu Journal databases were exhaustively searched using combinations of keywords relating to CTLA-4, MDR1 and UC. The published studies were filtered using our stringent inclusion and exclusion criteria, the quality assessment for each eligible study was conducted using Critical Appraisal Skill Program and the resultant high-quality data from final selected studies were analyzed using Comprehensive Meta-analysis 2.0 (CMA 2.0) software. The correlations between SNPs of CTLA-4 gene, MDR1 gene and the risk of UC were evaluated by OR at 95%CI. Z test was carried out to evaluate the significance of overall effect values. Cochran's Q-statistic and I(2) tests were applied to quantify heterogeneity among studies. Funnel plots, classic fail-safe N and Egger's linear regression test were inspected for indication of publication bias.
  
  
  RESULTS
  A total of 107 studies were initially retrieved and 12 studies were eventually selected for meta-analysis. These 12 case-control studies involved 1860 UC patients and 2663 healthy controls. Our major result revealed that single nucleotide polymorphisms (SNPs) of CTLA-4 gene rs3087243 G > A and rs231775 G > A may increase the risk of UC (rs3087243 G > A: allele model: OR = 1.365, 95%CI: 1.023-1.822, P = 0.035; dominant model: OR = 1.569, 95%CI: 1.269-1.940, P < 0.001; rs231775 G > A: allele model: OR = 1.583, 95%CI: = 1.306-1.918, P < 0.001; dominant model: OR = 1.805, 95%CI: 1.393-2.340, P < 0.001). In addition, based on our result, SNPs of MDR1 gene rs1045642 C > T might also confer a significant increases for the risk of UC (allele model: OR = 1.389, 95%CI: 1.214-1.590, P < 0.001; dominant model: OR = 1.518, 95%CI: 1.222-1.886, P < 0.001).
  
  
  CONCLUSIONS
  CTLA-4 gene rs3087243 G > A and rs231775 G > A, and MDR1 gene rs1045642 C > T might confer an increase for UC risk.
authors.affiliation: Jia-Jun Zhao, Di Wang, Hui Yao, Da-Wei Sun, Hong-Yu Li, Department of Gastroenterology, the General Hospital of Shenyang Military Region, Shenyang 110016, Liaoning Province, China.
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Zhao
authors.affiliation: Jia-Jun Zhao, Di Wang, Hui Yao, Da-Wei Sun, Hong-Yu Li, Department of Gastroenterology, the General Hospital of Shenyang Military Region, Shenyang 110016, Liaoning Province, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.affiliation: Jia-Jun Zhao, Di Wang, Hui Yao, Da-Wei Sun, Hong-Yu Li, Department of Gastroenterology, the General Hospital of Shenyang Military Region, Shenyang 110016, Liaoning Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.affiliation: Jia-Jun Zhao, Di Wang, Hui Yao, Da-Wei Sun, Hong-Yu Li, Department of Gastroenterology, the General Hospital of Shenyang Military Region, Shenyang 110016, Liaoning Province, China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Sun
authors.affiliation: Jia-Jun Zhao, Di Wang, Hui Yao, Da-Wei Sun, Hong-Yu Li, Department of Gastroenterology, the General Hospital of Shenyang Military Region, Shenyang 110016, Liaoning Province, China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Li
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D060908:CTLA-4 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016014:Linear Models; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human
keywords: Cytotoxic T lymphocyte-associated antigen-4; Meta-analysis; Multi-drug resistance 1; Polymorphism; Ulcerative colitis; rs1045642 C > T; rs231775 G > A; rs3087243 G > A