A functional interleukin-10 mutation in Dutch patients with Crohn's disease (original) (raw)
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World journal of gastroenterology : WJG, 2006
To examine the contribution of interleukin-10 (IL-10) gene polymorphisms to Crohnos disease (CD) phenotype, and the possible genetic epistasis between IL-10 gene polymorphisms and CARD15/NOD2 gene mutations. A cohort of 205 Spanish unrelated patients with Crohn's disease recruited from a single center was studied. All patients were rigorously phenotyped and followed-up for at least 3 years (mean time, 12.5 years). The clinical phenotype was established prior to genotyping. The correlation of genotype-Vienna classification groups showed that the ileocolonic location was significantly associated with the -1082G allele in the NOD2/CARD15 mutation-positive patients (RR=1.52, 95%CI, 1.21 to 1.91, P=0.008). The multivariate analysis demonstrated that the IL-10 G14 microsatellite allele in the NOD2/CARD15 mutation positive patients was associated with two risk factors, history of appendectomy (RR=2.15, 95%CI=1.1-4.30, P=0.001) and smoking habit at diagnosis (RR=1.29, 95%CI=1.04-4.3, P=...
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...
Inflammatory Bowel Disease and Mutations Affecting the Interleukin-10 Receptor
New England Journal of Medicine, 2009
METHODS-We performed genetic-linkage analysis and candidate-gene sequencing on samples from two unrelated consanguineous families with children who were affected by early-onset inflammatory bowel disease. We screened six additional patients with early-onset colitis for mutations in two candidate genes and carried out functional assays in patients' peripheral-blood mononuclear cells. We performed an allogeneic hematopoietic stem-cell transplantation in one patient.
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.
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.
IL4 , IL10 , IL16 , and TNF polymorphisms in New Zealand Caucasian Crohn’s disease patients
International Journal of Colorectal Disease, 2008
Dear Editor:Crohn’s disease (CD; OMIM 266600) is a multi-factorial, polygenic disease characterized by differential production of a number of cytokines that potentially contribute to the inflammatory response within the gut. Gene transcription of tumor necrosis factor (TNF; previously known as TNF-α; OMIM 191160; IBD3 locus) is increased in the intestinal mucosa of CD patients even in remission, and high levels of TNF are present in the serum, intestinal mucosa, and stool samples of CD patients. The −308G/A polymorphism (also known as TNF2) in the promoter region of the TNF gene was associated with increased levels of TNF in the plasma of cancer patients [Warzocha et al. (1998) Genetic polymorphisms in the TNF locus influence non-Hodgkin’s lymphoma outcome. Blood 91:3574–3581]. Peripheral blood mononuclear cells from CD patients homozygous for the AA alleles secrete more TNF than those of GG homozygotes, upon stimulation with T cell activators. The A allele is more frequent in subgroup