Association between polymorphisms in the promoter region of interleukin-10 and susceptibility to inflammatory bowel disease

Abstract

The aim of this study was to assess the association of polymorphisms in the promoter region of the IL-10 gene with the risk of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Fifteen studies (3,693 cases and 4,574 controls) were included in a meta-analysis of association between IL-10 -1082G/A, -819C/T and -592C/A polymorphisms, and IBD, CD and UC using allele contrast and the recessive, dominant, and additive models. Hardy-Weinberg equilibrium was confirmed for each study. Heterogeneity and study quality were investigated using stratification analyses and sensitivity analyses. Polymorphism -1082G/A showed significant association with CD, with odds ratios (ORs) for the GG + GA genotype and GG versus AA genotype of 1.278 (1.004-1.627) and 1.238 (1.027-1.492) in all subjects. Significant associations were found in the Caucasian subgroup using the allele contrast, dominant, and additive models. C-allele carriers of the -819C/T polymorphism were at increased risk of IBD (OR 1.093, 95% CI 1.004-1.190). Association with the -819C/T polymorphism was also found in Caucasians with CD (C vs. T: OR 1.104, 95% CI 1.010-1.206; CC + CT vs. TT: OR 1.328, 95% CI 1.006-1.754; CC vs. TT: OR 1.339, 95% CI 1.008-1.778), and with UC (CC vs. CT + TT: OR 1.188, 95% CI 1.019-1.385). No significant association was found between the -592C/A polymorphism and IBD, CD or UC. In conclusion, the meta-analysis demonstrated clear association between the IL-10 polymorphisms -1082G/A and -819C/T and the risk of IBD.

Inflammatory Bowel Disease: The Association of Inflammatory Cytokine Gene Polymorphisms

“…On the other hand, no significant association was found either with alleles or genotypes of -1082 G/A polymorphism and UC in Saudi patients. These results are in accordance with the various reports, which also indicted an association of IL-10-1082G/A polymorphism susceptibility to IBD [89,122]. A meta-analysis including 18 case-control studies provided evidence for the association between IL-10-1082G/ A polymorphism and susceptibility of CD [122].…”

“…A meta-analysis including 18 case-control studies provided evidence for the association between IL-10-1082G/ A polymorphism and susceptibility of CD [122]. Another met-analysis including 15 studies demonstrated clear association between the IL-10-1082G/A polymorphisms and the risk of IBD [89]. The allele G of -1082G/A polymorphism has been associated with the IBD, and higher serum levels of IL-10 concentration have been reported in IBD patients than in the controls [72,90].…”

“…Studies on the IL-10 promoter polymorphisms and IBD susceptibility have also been inconsistent [71,[83][84][85][86][87][88][89]. Some studies have found an associations between IL-10 polymorphism and IBD [71,86,87,90], whereas other studies were unable to find any association between IBD and the IL-10 promoter polymorphisms [83,84,88,91].…”

The Polymorphism rs3024505 (C/T) Downstream of the <i>IL10 </i>Gene Is Associated with Crohn’s Disease in Serbian Patients with Inflammatory Bowel Disease

“…However, most studies failed to find any association between IL10 promoter SNPs and susceptibility to develop IBD (Klein et al 2000;Koss et al 2000;Kim et al 2003;Balding et al 2004;Cantor et al 2005;Klausz et al 2005;Celik et al 2006;Sanchez et al 2009;Andersen et al 2010;Ahirwar et al 2012;Doecke et al 2013;Bank et al 2014;LopezHernandez et al 2015). Moreover, three meta-analysis, performed so far, were not consistent either, with each one showing associations of some of the three SNPs with one form of IBD that were not replicated by others (Zhu et al 2013;Lv et al 2014;Zou et al 2014). Interestingly, GWAS analyses did not find any evidence of association for those SNPs in IL10 promoter region with UC or CD (Barrett et al 2008;Franke et al 2008).…”

“…Functional significance of these polymorphisms have been demonstrated both in vitro (Turner et al 1997;Tagore et al 1999) and in vivo (Ouma et al 2008), associating GCC haplotype with high, ACC with intermediate and ATA haplotype with low IL-10 production. A number of studies in different populations and three meta-analyses have addressed the association of one or more of these SNPs in IL10 promoter region with IBD, but the results were inconsistent (Zhu et al 2013;Lv et al 2014;Zou et al 2014). Thus, the role of these three common IL10 SNPs in IBD susceptibility, although probable, has not been elucidated yet.…”