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Meta-Analysis
. 2013 Nov 13;8(11):e80602.
doi: 10.1371/journal.pone.0080602. eCollection 2013.

Association between variants of the autophagy related gene--IRGM and susceptibility to Crohn's disease and ulcerative colitis: a meta-analysis

Xiao Cheng Lu  1 , Yi Tao, Chen Wu, Peng Lai Zhao, Kai Li, Jin Yu Zheng, Li Xin Li
Affiliations
Meta-Analysis

Association between variants of the autophagy related gene--IRGM and susceptibility to Crohn's disease and ulcerative colitis: a meta-analysis

Xiao Cheng Lu et al. PLoS One. .

Abstract

Background: Polymorphisms in immunity-related GTPase family M (IRGM) gene may be associated with inflammatory bowel disease (IBD) by affecting autophagy. However, the genetic association studies on three common variants in IRGM gene (rs13361189, rs4958847 and rs10065172) have shown inconsistent results.

Methodology/ principal findings: The PubMed and Embase were searched up to June 5, 2013 for studies on the association between three IRGM polymorphisms and IBD risk. Data were extracted and the odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Finally, we performed a meta-analysis of 25 eligible studies in 3 SNPs located at IRGM gene by using a total of 20590 IBD cases and 27670 controls. The analysis showed modest significant association for the rs13361189, rs4958847 and rs10065172 variants in Crohn's disease (CD): the risk estimates for the allele contrast were OR=1.306 (1.200-1.420), p=5.2 × 10(-10), OR=1.182 (1.082-1.290), p=0.0002, and OR=1.248 (1.057-1.473), p=0.009 respectively (still significant when the p value was Bonferroni adjusted to 0.017). When stratified by ethnicity, significantly increased CD risk was observed in Europeans, but not in Asians. Conversely, there was no association of rs13361189 or rs4958847 variant with risk of ulcerative colitis (UC).

Conclusions/ significance: These results indicated that autophagy gene-IRGM polymorphisms appear to confer susceptibility to CD but not UC, especially in Europeans. Our data may provide further understanding of the role of autophagy in the pathogenesis of CD.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Flowchart of search strategy for meta-analysis.
Figure 2
Figure 2. Allele frequencies (%) in the three major ethnical groups in controls of CD to (A) rs13361189, (B) rs4958847 and (C) rs10065172.
Each data point represents a separate study for the indicated association. Horizontal line represents the mean value.
Figure 3
Figure 3. OR estimates with the corresponding 95% CI for the associations between IRGM polymorphisms ((A) rs13361189, (B) rs4958847, and (C) rs10065172) and the risk of CD (dominant model).
The sizes of the squares reflect the weighting of included studies; the centre of diamonds reflect summary effect, the left and right extremes of diamonds reflect 95% confidence intervals; CI, confidence interval; OR, odds ratio.
Figure 4
Figure 4. Sensitivity analysis on the associations between IRGM polymorphisms ((A) rs13361189, (B) rs4958847, and (C) rs10065172) and CD risk (dominant model).
Results were computed by omitting each study (left column) in turn, Bars: 95% confidence interval.
Figure 5
Figure 5. Cumulative meta-analysis: pooled OR with the corresponding 95% CI at the end of each year information step is shown for IRGM polymorphisms ((A) rs13361189, (B) rs4958847, and (C) rs10065172) and risk of CD (dominant model).
See this image and copyright information in PMC

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Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (No. 30973092 and No. 81178147), “Xingwei Project” Key Personal Medical Research Foundation of Health Department of Jiangsu Province (No. RC201156), “Six Categories of Key Person” Research Foundation of Jiangsu Province (No. 069), Program Sponsored for Scientific Innovation Research of College Graduate in Jiangsu Province (No. CXZZ12_0583), and Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (No. JX10231801). grants from the National Natural Science Foundation of China (No. 30973092 and No. 81178147)", replace 81178147 with 81171147. - In ACs, add author Kai Li to "analyzed the data" and "contributed reagents. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.