Meta-Analysis
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2015; 21(34): 10025-10040
Published online Sep 14, 2015. doi: 10.3748/wjg.v21.i34.10025
CTLA-4 and MDR1 polymorphisms increase the risk for ulcerative colitis: A meta-analysis
Jia-Jun Zhao, Di Wang, Hui Yao, Da-Wei Sun, Hong-Yu Li
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
Author contributions: Zhao JJ and Wang D performed the majority of experiments; Yao H provided vital reagents and analytical tools and were also involved in editing the manuscript; Sun DW co-ordinated and provided the collection of all the human material in addition to providing financial support for this work; Li HY designed the study and wrote the manuscript.
Conflict-of-interest statement: The declaration of the authors reveals that they have not received any financial payments or other benefits from any commercial entity associated with the subject of this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Hong-Yu Li, Department of Gastroenterology, the General Hospital of Shenyang Military Region, No. 83, Wenhua Road, Shenhe District, Shenyang 110016, Liaoning Province, China. lihongyu0913@126.com
Telephone: +86-24-28851113 Fax: +86-24-28851113
Received: January 6, 2015
Peer-review started: January 7, 2015
First decision: January 22, 2015
Revised: February 26, 2015
Accepted: May 4, 2015
Article in press: May 4, 2015
Published online: September 14, 2015
Abstract

AIM: 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 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 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).

CONCLUSION: CTLA-4 gene rs3087243 G > A and rs231775 G > A, and MDR1 gene rs1045642 C > T might confer an increase for UC risk.

Keywords: Ulcerative colitis, Cytotoxic T lymphocyte-associated antigen-4, Multi-drug resistance 1, rs3087243 G > A, rs231775 G > A, rs1045642 C > T, Polymorphism, Meta-analysis

Core tip: 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. CTLA-4 gene rs3087243 G > A and rs231775 G > A, and MDR1 gene rs1045642 C > T might confer an increases for UC risk.