Development of a uniform, very aggressive disease phenotype in all homozygous carriers of the NOD2 mutation p.Leu1007fsX1008 with Crohn’s disease and active smoking status resulting in ileal stenosis requiring surgery

NOD2 variants are the strongest genetic predictors for susceptibility to Crohn's disease (CD). However, the clinical value of NOD2 on an individual patient level remains controversial. We aimed to define the predictive power of the major NOD2 mutations regarding complicated CD in a large single...

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Bibliographic Details
Published in:PloS one 2020-07, Vol.15 (7), p.e0236421-e0236421
Main Authors: Schnitzler, Fabian, Friedrich, Matthias, Angelberger, Marianne, Diegelmann, Julia, Stallhofer, Johannes, Wolf, Christiane, Dütschler, Joel, Truniger, Samuel, Olszak, Torsten, Beigel, Florian, Tillack, Cornelia, Lohse, Peter, Brand, Stephan
Format: Article
Language:English
Subjects:
Age
Biology and Life Sciences
Biomarkers
Cigarette smoking
Complications and side effects
Crohn's disease
Disease
Drug addiction
Frameshift mutation
Gastroenterology
Gene frequency
Gene mutation
Genetic aspects
Genotype & phenotype
Genotypes
Health aspects
Hepatology
Homozygosity
Immunosuppressive agents
Medicine
Medicine and Health Sciences
Mutation
NOD2
NOD2 protein
Ostomy
Patients
Phenotypes
Rheumatology
Risk factors
Smoking
Stenosis
Studies
Surgery
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Summary:NOD2 variants are the strongest genetic predictors for susceptibility to Crohn's disease (CD). However, the clinical value of NOD2 on an individual patient level remains controversial. We aimed to define the predictive power of the major NOD2 mutations regarding complicated CD in a large single center cohort. 1076 CD patients were prospectively genotyped for the three common CD-associated NOD2 mutations rs2066844, rs2066845, and rs2066847, followed by detailed genotype-phenotype analyses. Overall, 434 CD patients (40.3%) carried at least one of the three main NOD2 mutations. A significantly higher minor allele frequency (15.6%) of the NOD2 frameshift mutation p.Leu1007fsX1008 (rs2066847) was seen in patients with aggressive disease compared to 8.2% in patients with mild disease (p = 2.6 x 10.sup.-5). Moreover, a total of 54 CD patients (5.0%) were homozygous for this NOD2 frameshift mutation. 100% of these patients had ileal disease compared to 82% of NOD2 wild-type carriers (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0236421