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Molecular prediction of disease risk and severity in a large Dutch Crohn's disease cohort
- Source :
- Gut, 58(3), 388-395. BMJ Publishing Group, Gut, 58, 388-95, Gut, 58, 3, pp. 388-95, Weersma, R L S, Stokkers, P C, van Bodegraven, A A, Hogezand, R J P, Verspaget, H W, Jong, D, van der Woude, C J, Oldenburg, B, Linskens, R K, Festen, E A, van der Steege, G, Hommes, D W, Crusius, J B A, Wijmenga, C, Nolte, I & Dijkstra, G 2009, ' Molecular prediction of disease risk and severity in a large Dutch Crohn's disease cohort ', Gut, vol. 58, no. 3, pp. 388-395 . https://doi.org/10.1136/gut.2007.144865, Gut, 58(3), 388-395. BMJ PUBLISHING GROUP
- Publication Year :
- 2009
-
Abstract
- Background: Crohn’s disease and ulcerative colitis have a complex genetic background. We assessed the risk for both the development and severity of the disease by combining information from genetic variants associated with inflammatory bowel disease (IBD). Methods: We studied 2804 patients (1684 with Crohn’s disease and 1120 with ulcerative colitis) and 1350 controls from seven university hospitals. Details of the phenotype were available for 1600 patients with Crohn’s disease and for 800 with ulcerative colitis. Genetic association for disease susceptibility was tested for the nucleotide-binding and oligomerisation domain 2 gene (NOD2), the IBD5 locus, the Drosophila discs large homologue 5 and autophagy-related 16-like 1 genes (DLG5 and ATG16L1) and the interleukin 23 receptor gene (IL23R). Interaction analysis was performed for Crohn’s disease using the most associated single nucleotide polymorphism (SNP) for each locus. Odds ratios were calculated in an ordinal regression analysis with the number of risk alleles as an independent variable to analyse disease development and severity. Results: Association with Crohn’s disease was confirmed for NOD2, IBD5, DLG5, ATG16L1 and IL23R. Patients with Crohn’s disease carry more risk alleles than controls (p = 3.85 6 10 222 ). Individuals carrying an increasing number of risk alleles have an increasing risk for Crohn’s disease, consistent with an independent effects multiplicative model (trend analysis p = 4.25 6 10 223 ). Patients with Crohn’s disease with a more severe disease course, operations or an age of onset below 40 years have more risk alleles compared to non-stricturing, nonpenetrating behaviour (p = 0.0008), no operations (p = 0.02) or age of onset above 40 years (p = 0.028). Conclusion: Crohn’s disease is a multigenic disorder. An increase in the number of risk alleles is associated with an increased risk for the development of Crohn’s disease and with a more severe disease course. Combining information from the known common risk polymorphisms may enable clinicians to predict the course of Crohn’s disease. Chronic inflammatory bowel diseases (IBDs) comprising Crohn’s disease and ulcerative colitis are characterised by chronic recurring inflammation of the gastrointestinal tract. The combined prevalence of Crohn’s disease and ulcerative colitis is estimated at 100/100 000 to 200/100 000 in developed countries.
- Subjects :
- Interleukin-23 receptor
Male
Nod2 Signaling Adaptor Protein
ATG16L1
Disease
VARIANTS
Gastroenterology
Inflammatory bowel disease
0302 clinical medicine
Crohn Disease
NOD2
MULTIPLE
Odds Ratio
Netherlands
0303 health sciences
Crohn's disease
GENETIC-VARIATION
Ulcerative colitis
3. Good health
Pathogenesis and modulation of inflammation [N4i 1]
ULCERATIVE-COLITIS
030211 gastroenterology & hepatology
AUTOPHAGY
Female
Adult
medicine.medical_specialty
SUSCEPTIBILITY LOCI
Genotype
Risk Assessment
03 medical and health sciences
Internal medicine
medicine
Humans
Genetic Predisposition to Disease
GENOME-WIDE ASSOCIATION
Molecular Biology
POLYMORPHISMS
Alleles
030304 developmental biology
Polymorphism, Genetic
business.industry
Receptors, Interleukin
medicine.disease
digestive system diseases
Gene Expression Regulation
Immunology
Colitis, Ulcerative
Age of onset
business
INFLAMMATORY-BOWEL-DISEASE
Subjects
Details
- ISSN :
- 00175749
- Database :
- OpenAIRE
- Journal :
- Gut, 58(3), 388-395. BMJ Publishing Group, Gut, 58, 388-95, Gut, 58, 3, pp. 388-95, Weersma, R L S, Stokkers, P C, van Bodegraven, A A, Hogezand, R J P, Verspaget, H W, Jong, D, van der Woude, C J, Oldenburg, B, Linskens, R K, Festen, E A, van der Steege, G, Hommes, D W, Crusius, J B A, Wijmenga, C, Nolte, I & Dijkstra, G 2009, ' Molecular prediction of disease risk and severity in a large Dutch Crohn's disease cohort ', Gut, vol. 58, no. 3, pp. 388-395 . https://doi.org/10.1136/gut.2007.144865, Gut, 58(3), 388-395. BMJ PUBLISHING GROUP
- Accession number :
- edsair.doi.dedup.....f2e83af8da752b32abc407cefe2abc9e
- Full Text :
- https://doi.org/10.1136/gut.2007.144865