Meta-Analysis
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2015; 21(28): 8711-8722
Published online Jul 28, 2015. doi: 10.3748/wjg.v21.i28.8711
Interleukin-18 genetic polymorphisms contribute differentially to the susceptibility to Crohn’s disease
Su-Jun Gao, Li Zhang, Wei Lu, Lu Wang, Lei Chen, Zhen Zhu, Hai-Hang Zhu
Su-Jun Gao, Li Zhang, Wei Lu, Lu Wang, Lei Chen, Zhen Zhu, Hai-Hang Zhu, Department of Gastroenterology, Subei People’s Hospital, Yangzhou 225001, Zhejiang Province, China
Author contributions: Gao SJ, Zhang L and Lu W designed the study, analyzed data and wrote the manuscript as co-first authors; Zhang L contributed to the discussions and wrote the manuscript; Wang L, Chen L and Zhu Z edited the manuscript; Lu W and Zhu HH designed the study, contributed to the discussions and edited the manuscript as a corresponding author; Gao SJ, Zhang L and Lu W contributed equally to this article as first author(s).
Conflict-of-interest statement: The authors have declared that they have no competing interests.
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. Hai-Hang Zhu, Department of Gastroenterology, Subei People’s Hospital, No. 98 Nantong Street, Yangzhou 225001, Zhejiang Province, China. doczhuhaihang@163.com
Telephone: +86-514-87373385 Fax: +86-514-87373385
Received: August 22, 2014
Peer-review started: August 23, 2014
First decision: October 29, 2014
Revised: December 5, 2014
Accepted: March 12, 2015
Article in press: March 12, 2015
Published online: July 28, 2015
Abstract

AIM: To investigate the correlation between interleukin-18 (IL-18) gene polymorphisms and the risk of developing Crohn’s disease (CD).

METHODS: The PubMed, CISCOM, CINAHL, Web of Science, EBSCO, Cochrane Library, MEDLINE, EMBASE and CBM databases were searched without any language restrictions using combinations of keywords relating to CD and IL-18 for relevant articles published before November 1st, 2013. Screening of the published studies retrieved from searches was based on our stringent inclusion and exclusion criteria and resulted in seven eligible studies for meta-analysis. A meta-analysis was conducted using a random-effects model with STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (95%CI) were calculated.

RESULTS: Seven case-control studies, with a total of 1930 CD cases and 1930 healthy subjects, met our inclusion criteria. The results of our meta-analysis indicated that the IL-18 rs1946518 A>C and rs187238 G>C polymorphisms may correlate with an increased risk of CD under five genetic models (all P < 0.05). Furthermore, we observed positive associations between the IL-18 rs360718 A>C polymorphism and CD risk under three genetic models (C allele vs A allele: OR = 2.03, 95%CI: 1.20-3.43, P = 0.008; CC vs AA+AC: OR = 2.39, 95%CI: 1.2-4.43, P = 0.006; CC vs AC: OR = 2.31, 95%CI: 1.22-4.38, P = 0.010). However, such associations were not found for the IL-18 rs917997 C>T, codon 35 A>C and rs1946519 G>T polymorphisms (all P > 0.05). A subgroup analysis was conducted to investigate the effect of ethnicity on an individual’s susceptibility to CD. Our results revealed positive correlations between IL-18 genetic polymorphisms and an increased risk of CD among Asians and Africans (all P < 0.05), but not among Caucasians (all P > 0.05).

CONCLUSION: This meta-analysis indicated that the IL-18 rs1946518 A>C, rs187238 G>C and rs360718 A>C polymorphisms may contribute to susceptibility to CD, especially among Asians and Africans. These polymorphisms are known to reduce IL-18 mRNA and protein levels.

Keywords: Interleukin-18, Single nucleotide polymorphism, Crohn’s disease, Meta-analysis

Core tip: This meta-analysis was performed to evaluate the relationships between genetic polymorphisms in the Interleukin-18 gene and the risk of developing Crohn’s disease.