Dataset Information

The NOD2 Single Nucleotide Polymorphism rs72796353 (IVS4+10 A>C) Is a Predictor for Perianal Fistulas in Patients with Crohn's Disease in the Absence of Other NOD2 Mutations.

ABSTRACT:

Background

A previous study suggested an association of the single nucleotide polymorphism (SNP) rs72796353 (IVS4+10 A>C) in the NOD2 gene with susceptibility to Crohn's disease (CD). However, this finding has not been confirmed. Given that NOD2 variants still represent the most important predictors for CD susceptibility and phenotype, we evaluated the association of rs72796353 with inflammatory bowel disease (IBD) susceptibility and the IBD phenotype.

Methodology

Genomic DNA from 2256 Caucasians, including 1073 CD patients, 464 patients with ulcerative colitis (UC), and 719 healthy controls, was genotyped for the NOD2 SNP rs72796353 and the three main CD-associated NOD2 mutations rs2066844, rs2066845, and rs2066847. Subsequently, IBD association and genotype-phenotype analyses were conducted.

Results

In contrast to the strong associations of the NOD2 SNPs rs2066844 (p=3.51 x 10(-3)), rs2066845 (p=1.54 x 10(-2)), and rs2066847 (p=1.61 x 10(-20)) with CD susceptibility, no significant association of rs72796353 with CD or UC susceptibility was found. However, in CD patients without the three main CD-associated NOD2 mutations, rs72796353 was significantly associated with the development of perianal fistulas (p=2.78 x 10(-7), OR 5.27, [95% CI 2.75-10.12] vs. NOD2 wild-type carriers).

Conclusion/significance

Currently, this study represents the largest genotype-phenotype analysis of the impact of the NOD2 variant rs72796353 on the disease phenotype in IBD. Our data demonstrate that in CD patients the IVS4+10 A>C variant is strongly associated with the development of perianal fistulas. This association is particularly pronounced in patients who are not carriers of the three main CD-associated NOD2 mutations, suggesting rs72796353 as additional genetic marker for the CD disease behaviour.

SUBMITTER: Schnitzler F

PROVIDER: S-EPMC4493062 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The NOD2 Single Nucleotide Polymorphism rs72796353 (IVS4+10 A>C) Is a Predictor for Perianal Fistulas in Patients with Crohn's Disease in the Absence of Other NOD2 Mutations.

Schnitzler Fabian F Friedrich Matthias M Wolf Christiane C Stallhofer Johannes J Angelberger Marianne M Diegelmann Julia J Olszak Torsten T Tillack Cornelia C Beigel Florian F Göke Burkhard B Glas Jürgen J Lohse Peter P Brand Stephan S

PloS one 20150706 7

<h4>Background</h4>A previous study suggested an association of the single nucleotide polymorphism (SNP) rs72796353 (IVS4+10 A>C) in the NOD2 gene with susceptibility to Crohn's disease (CD). However, this finding has not been confirmed. Given that NOD2 variants still represent the most important predictors for CD susceptibility and phenotype, we evaluated the association of rs72796353 with inflammatory bowel disease (IBD) susceptibility and the IBD phenotype.<h4>Methodology</h4>Genomic DNA from ...[more]

PMID: 26147989

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Project description:IntroductionA high prevalence of cryptoglandular and Crohn's perianal fistulas has been reported worldwide, and several surgical options are available for the management of anal fistula, with varying clinical efficacy. However, currently, the available evidence for the effectiveness of these surgical approaches are lacking and of concern in terms of the credibility and strength. The purpose of this study is to evaluate the credibility of the published systematic reviews and meta-analyses that assess the efficacy and safety of the surgical options for cryptoglandular and Crohn's perianal fistulas through an umbrella review.Methods and analysisA systematic search in PubMed, Embase and Cochrane library will be performed from inception to December 2020 without any language restriction. We will include systematic reviews and meta-analyses that investigate the efficacy and safety of surgical approaches in the management of cryptoglandular and Crohn's perianal fistulas. Two reviewers will independently screen search results through reading the titles or abstracts. Relevant information will be extracted from each eligible systematic review or meta-analysis. Based on random effects model summary estimates along with their p values, 95% prediction intervals, between-study heterogeneity, small-study effects and excess significance, we will classify the evidence from convincing (class I) to weak (class IV). Findings will be summarized using quantitative synthesis combined with a narrative approach. Cryptoglandular and Crohn's perianal fistulas will be summarized separately. Two authors will independently perform the literature search, data extraction, and quality assessment of each included systematic review and meta-analysis. Any unresolved conflicts or doubts will be resolved by discussion or by consulting a senior author. The risk of bias of the systematic reviews will be assessed using a 16-item Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklist. The strength of evidence for the included systematic reviews will be classified as "high", "moderate", "low", or "critically low" quality.Ethics and disseminationEthics approval is not required as we will collect data from the published systematic reviews and meta-analyses without using individual patient data. The results of this umbrella review will be published in a peer-reviewed journal and will be presented at an anorectal disease conference.Prospero registration numberCRD42020200754.

Dataset Information

The NOD2 Single Nucleotide Polymorphism rs72796353 (IVS4+10 A>C) Is a Predictor for Perianal Fistulas in Patients with Crohn's Disease in the Absence of Other NOD2 Mutations.

Background

Methodology

Results

Conclusion/significance

Publications

The NOD2 Single Nucleotide Polymorphism rs72796353 (IVS4+10 A>C) Is a Predictor for Perianal Fistulas in Patients with Crohn's Disease in the Absence of Other NOD2 Mutations.

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