The IL-10 gene is not involved in the predisposition to inflammatory bowel disease

Klein, Wolfram; Tromm, Andreas; Griga, Thomas; Fricke, Harald; Folwaczny, C; Hocke, Michael; Eitner, K; Marx, Michaela; Runte, Maren; Epplen, Jörg T.

doi:10.1002/1522-2683(200011)21:17<3578::aid-elps3578>3.3.co;2-q

Cited by 15 publications

(24 citation statements)

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“…These findings led to the hypothesis that mucosal healing in inflammatory bowel disease upon IL-10 treatment could be dependent on genetic variations between subgroups of patients. Previous work has explored the possibility that the polymorphic nature of the IL-10 promoter region might be associated with intestinal inflammation in particular subgroups of patients (23)(24)(25). We chose to screen for mutations in the IL-10R1 and detected two novel variants that were shown to meet the criteria of coding single nucleotide polymorphisms (cSNPs).…”

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confidence: 99%

Novel Variants of the IL-10 Receptor 1 Affect Inhibition of Monocyte TNF-α Production

Gasché

Grundtner

Zwirn

et al. 2003

The Journal of Immunology

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IL-10-deficient mice exhibit spontaneous enterocolitis and other symptoms akin to Crohn’s disease, indicating that IL-10 might regulate normal physiology in the gut. However, clinical trials with IL-10 in Crohn’s disease were disappointing, although some patients showed healing of intestinal mucosa. This study searched for genetic polymorphisms within the IL-10 pathway. We decided to screen for mutations of the IL-10R1 cDNA in healthy volunteers and Crohn’s disease patients and identified two novel variants: a serine 138-to-glycine (S138G) and a glycine 330-to-arginine (G330R) substitution. The allelic frequency in a European cohort was relatively high (16% for the S138G and 33% for the G330R), and S138G was in strong linkage disequilibrium with G330R. A similar allele frequency was found in a group of Crohn’s patients. In IL-10R1 G330R-expressing monocytes, the inhibitory effect of IL-10 on TNF-α production was diminished, indicating that this variant may be a loss-of-function allele. No such difference was observed between haplotypes 4 (G330R only) and 7 (S138G and G330R). In addition, these IL-10R1 variants had no influence on the IL-10R1 expression density. Structural analysis of the S138G variant revealed that the substitution of S138G may interfere with binding of IL-10 to IL-10R1.

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confidence: 99%

Novel Variants of the IL-10 Receptor 1 Affect Inhibition of Monocyte TNF-α Production

Gasché

Grundtner

Zwirn

et al. 2003

The Journal of Immunology

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“…Contrary to these, some studies reported that there are no significant differences in the allele and genotype frequencies of the IL-10-1082G/A polymorphism between IBD patients and controls in various populations [88,91,120]. Klein et al [91] reported that IL-10-1082G/A polymorphism is not demonstrably involved in the predisposition of IBD in German cohort.…”

Section: Discussionmentioning

confidence: 92%

“…Klein et al [91] reported that IL-10-1082G/A polymorphism is not demonstrably involved in the predisposition of IBD in German cohort. Similarly, no association between Turkish IBD patients and IL-10-1082G/A was found [120].…”

Section: Discussionmentioning

confidence: 99%

“…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]. In this study, we evaluated the association of five polymorphism in IL-10, TNF-α, and TNF-β genes with susceptibility risk of IBD in Saudi patients.…”

Section: Introductionmentioning

confidence: 96%

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Inflammatory Bowel Disease: The Association of Inflammatory Cytokine Gene Polymorphisms

Al-Robayan¹,

Arfin²,

Meghaiseeb³

et al. 2016

New Insights Into Inflammatory Bowel Disease

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“…The polymorphism C-592A was also associated with CD in Canadian pediatric patients (Amre et al 2009). 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).…”

Section: Discussionmentioning

confidence: 99%

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

Mijač

Petrović

Djuranović

et al. 2016

Tohoku J. Exp. Med.

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Inflammatory bowel disease (IBD), manifesting as Crohn's disease (CD) and ulcerative colitis (UC), is characterized by recurring episodes of inflammation in gastrointestinal tract, in which aberrant production of regulatory cytokine interleukin-10 (IL-10) presumably plays important role. Single nucleotide polymorphisms (SNPs) that affect IL-10 production, such as rs1800896 (G/A) at position -1082 and rs1800871 (C/T) at position -819 in the promoter region of the IL10 gene, have been associated with CD and/or UC, but the results were inconsistent. Another SNP that may alter IL-10 production, rs3024505 (C/ T) located immediately downstream of the IL10 gene has been recently identified. T allele of rs3024505 was associated with both UC and CD in Western populations, but the studies from East European countries are lacking. Therefore, our aim was to assess the association of rs3024505, rs1800896 and rs1800871 with Serbian IBD patients. To this end, 107 CD and 99 UC patients and 255 healthy controls were genotyped. As a result, T allele of rs3024505 was associated with CD at allelic, genotypic (GT genotype) and haplotypic (GCCT haplotype) level, suggesting potential role of this variant in susceptibility to CD. In contrast, CD patients carrying C allele of rs3024505 had significantly increased risk of anemia and stricturing/penetrating behavior. No association was observed between rs3024505 and UC or SNPs in IL10 promoter region and any form of IBD. In conclusion, rs3024505 SNP flanking the IL10 gene is associated with susceptibility and severity of disease in Serbian CD patients, further validating its role as a potential biomarker in IBD.

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The IL-10 gene is not involved in the predisposition to inflammatory bowel disease

Cited by 15 publications

References 0 publications

Novel Variants of the IL-10 Receptor 1 Affect Inhibition of Monocyte TNF-α Production

Novel Variants of the IL-10 Receptor 1 Affect Inhibition of Monocyte TNF-α Production

Inflammatory Bowel Disease: The Association of Inflammatory Cytokine Gene Polymorphisms

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

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