Interleukin 10 ( IL-10 ) gene variants and susceptibility for paediatric onset Crohn’s disease (original) (raw)
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BMC Medical Genetics, 2010
Background: Crohns disease (CD) and ulcerative colitis (UC) are characterized by a dysregulated inflammatory response to normal constituents of the intestinal flora in the genetically predisposed host. Heme oxygenase-1 (HO-1/ HMOX1) is a powerful anti-inflammatory and anti-oxidant enzyme, whereas the pro-inflammatory interleukin 1β (IL-1β/ IL1B) and anti-inflammatory interleukin 10 (IL-10/IL10) are key modulators for the initiation and maintenance of inflammation. We investigated whether single nucleotide polymorphisms (SNPs) in the IL-1β, IL-10, and HO-1 genes, together with smoking, were associated with risk of CD and UC.
World journal of gastroenterology, 2017
To study the genetic association and epistatic interaction of the interleukin (IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease (IBD). A total of 159 pediatric inflammatory IBD patients (Crohn's disease, n = 136; ulcerative colitis, n = 23) and 129 matched controls were studied for genetic association of selected single nucleotide polymorphisms (SNPs) of the IL-10 gene and the genes IL10RA, IL10RB, STAT3, and HO1, from the IL-10/STAT3 signaling pathway. As interactions between SNPs from different loci may significantly affect the associated risk for disease, additive (a) and dominant (d) modeling of SNP interactions was also performed to examine high-order epistasis between combinations of the individual SNPs. The results showed that IL-10 rs304496 was associated with pediatric IBD (P = 0.022), but no association was found for two other IL-10 SNPs, rs1800872 and rs2034498, or for SNPs in genes IL10RA, IL10RB, STAT3, and HO1. However, analysis of epistatic ...
A functional interleukin-10 mutation in Dutch patients with Crohn's disease
Digestive and Liver Disease, 2005
Background and aims. Interleukin-10 is an anti-inflammatory and immunomodulatory cytokine. Interleukin-10 deficient mice are prone to develop chronic colitis. Administration of recombinant human interleukin-10 has been proposed to have a beneficial effect in a subgroup of patients with Crohn's disease. Recently, we found an interleukin-10 Gly15Arg mutation in a family with Crohn's disease which is associated with reduced interleukin-10 secretion by in vitro stimulated monocytes and lymphocytes. We hypothesised that this interleukin-10 mutation plays a role in maintaining the inflammatory process in Crohn's disease in some families. Patients and methods. We evaluated interleukin-10 Gly15Arg in 379 patients with Crohn's disease, and 75 unrelated healthy controls. Also, first degree family members of interleukin-10 Gly15Arg carriers were evaluated. Additionally, mutation carriers and their relatives were evaluated for CARD15 R702W, G908R, and 1007fs. Results. Two patients with Crohn's disease were heterozygous for the interleukin-10 Gly15Arg mutation. No homozygotes were found. The Gly15Arg mutation was not observed in the controls. In first degree family members of the Crohn's disease-affected interleukin-10 Gly15Arg carriers, the mutation was found in Crohn's disease-affected as well as in their apparently healthy individuals. All family members carried one or two CARD15 mutation(s). Conclusion. The interleukin-10 Gly15Arg mutation is rare in patients with Crohn's disease, and is not associated with the disease in the Netherlands.
Digestive diseases and sciences, 2001
Interleukin-10 (IL-10) has a key role in regulating mucosal inflammation. The role of functional polymorphisms at positions -627 and -1117 in the IL-10 gene as candidate susceptibility loci in inflammatory bowel disease and their importance in determining disease extent were evaluated in 159 patients with ulcerative colitis (83 left-sided; 76 extensive), 90 patients with Crohn's disease (22 small bowel; 29 large bowel; 39 both), and 227 controls. Genotyping was performed either by PCR-RFLP assays (-627 site) or SSCP analysis (-1117 site). An excess of -627A allele was observed in patients with left-sided colitis (52%) compared with controls (33%; P = 0.004) suggesting that IL-10 may influence the extent of the disease. These results were not replicated in a newly recruited group (N = 100) of patients with UC. We conclude that polymorphisms at -627 and -1117 sites in the IL-10 gene do not contribute to the susceptibility to IBD or determining the extent of the disease in our popu...
Interleukin 10 promoter region polymorphisms in inflammatory bowel disease in Tunisian population
Inflammation Research, 2009
Objective: To test whether IL-10 promoter region polymorphisms are associated with susceptibility to inflammatory bowel disease, we examined the contribution of interleukin- 10 (IL-10) gene polymorphisms to Crohn’s disease (CD) and Ulcerative colitis disease (UC) occurrence and also to CD phenotype. Materiels and Methods: SNPs at positions -627 (C > A) and −1117 (G > A) in the IL-10 promoter were determined in a sample of 105 Tunisian patients with IBD (75 CD and 30 UC) and 90 matched healthy controls. Results: The 627 CA genotype is associated with ileal location (p = 0.015) and with stricturing (p = 510-3) and penetrating (p = 310-3) presentation of CD. An additive effect between IL10 variants and CARD15 3020 insC mutation (p = 0,006) on severe forms of CD was shown. Conclusions: In Tunisian population, the 3020insC insertion in NOD2/CARD15 gene is a marker of susceptibility to CD, while the A allele at position -627 in the IL-10 promoter increases the risk of CD ileal location and severe disease presentation. A genetic epistasis between IL-10 gene polymorphisms and CARD15/NOD2 gene mutation was suggested.