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


RESULTS
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
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.
Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Xiao Cheng
XC
Lu
Yi
Y
Tao
Chen
C
Wu
Peng Lai
PL
Zhao
Kai
K
Li
Jin Yu
JY
Zheng
Li Xin
LX
Li
D000483:Alleles; D001343:Autophagy / Q000235:genetics*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017594:Publication Bias
D019204:GTP-Binding Proteins; C513539:IRGM protein, human