Abstract
The -173 G/C polymorphism in the macrophage migration inhibitory factor (MIF) gene has been implicated in susceptibility to inflammatory bowel disease (IBD), but the results are inconclusive. The present meta-analysis aimed to investigate the overall association between the -173 G/C polymorphism and IBD risk. We searched in Pubmed, and Embase for studies evaluating the association between the -173G/C gene polymorphism and IBD risk. Data were extracted and statistical analysis was performed using Revman 5.1 and STATA 12.0 software. A total of seven publications involving 4729 subjects (2282 IBD cases and 2447 controls) were included in this meta-analysis. Combined analysis revealed a clear association between this polymorphism and IBD susceptibility (OR = 1.48, 95% CI: 1.10–2.00, p = 0.009 for CC vs. CG + GG). Subgroup analysis by ethnicity showed that the IBD risk associated with the -173G/C gene polymorphism was significantly elevated among Asians (OR = 1.79, 95% CI: 1.08–2.96, p = 0.02), but not among Caucasians. Subgroup analysis by disease suggested that the -173G/C gene polymorphism is a risk factor for ulcerative colitis (OR = 1.62, 95% CI: 1.10–2.37, p = 0.01), but that it was not associated with Crohn’s disease. This meta-analysis suggests that the -173 G/C polymorphism in the macrophage MIF gene contributes to IBD susceptibility, specifically in Asian populations. Further studies are needed to validate these findings.
Highlights
Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), refers to a heterogeneous group of chronic disorders that leads to cachexia
These findings suggest a potential role for migration inhibitory factor (MIF) in IBD pathogenesis and treatment [8]; consistent with this notion, polymorphism in the MIF gene has been associated with susceptibility to inflammatory diseases, such as IBD [9]
A total of seven publications evaluating the association between the MIF -173G/C polymorphism and IBD risk were included in the meta-analysis, involving 4729 subjects (2282 IBDs cases and 2447 controls) [11,12,13,14,15,16,17]
Summary
Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), refers to a heterogeneous group of chronic disorders that leads to cachexia. IBD results from an abnormal inflammatory response, in which genetic and environmental factors play important roles [3]. Numerous studies have investigated the association of genetic variants with IBD susceptibility [4], and among them, the macrophage migration inhibitory factor (MIF) gene has been highlighted. DNA-vaccine targeting MIF may be a useful approach for the treatment of colitis including inflammatory bowel diseases [7] These findings suggest a potential role for MIF in IBD pathogenesis and treatment [8]; consistent with this notion, polymorphism in the MIF gene has been associated with susceptibility to inflammatory diseases, such as IBD [9]. Several studies have investigated whether the -173 G/C polymorphism in the macrophage MIF gene is associated with IBD risk, and the results have been inconsistent and inconclusive. Since pooled estimates based on meta-analysis have proven to be useful in determining the overall risk of certain IBD polymorphisms when results of individual studies are inconsistent [10], we decided to perform the present meta-analysis in order to clarify the association between the MIF -173G/C polymorphism and IBD risk
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