CTLA-4 and MDR1 polymorphisms increase the risk for ulcerative colitis:A meta-analysis

• Published in: World journal of gastroenterology : WJG Vol. 21; no. 34; pp. 10025 - 10040
• Main Authors: Zhao, Jia-Jun, Wang, Di, Yao, Hui, Sun, Da-Wei, Li, Hong-Yu
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 14.09.2015
• Subjects: ATP Binding Cassette Transporter, Sub-Family B - genetics; Case-Control Studies; Colitis, Ulcerative - diagnosis; Colitis, Ulcerative - genetics; colitis;Cytotoxic; CTLA-4 Antigen - genetics; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Linear Models; lymphocyte-associat; Meta-Analysis; Odds Ratio; Phenotype; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors; Ulcerative; rs3087243 G > A; Multi-drug resistance 1; rs1045642 C > T; Cytotoxic T lymphocyte-associated antigen-4; rs231775 G > A; Meta-analysis; Polymorphism; Ulcerative colitis
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v21.i34.10025

AIM:To evaluate the correlations between cytotoxic T lymphocyte-associated antigen-4(CTLA-4) and multidrug resistance 1(MDR1) genes polymorphisms with ulcerative colitis(UC) risk.METHODS:Pub Med,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 I2 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 metaanalysis. 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).CONCLUSION:CTLA-4 gene rs3087243 G > A and rs231775 G > A,and MDR1 gene rs1045642 C > T might confer an increase for UC risk.