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Molecular prediction of disease risk and severity in a large Dutch Crohn's disease cohort

Authors :
G. van der Steege
Dirk J. de Jong
R. K. Linskens
Bas Oldenburg
Pieter C. F. Stokkers
C.J. van der Woude
R. A. van Hogezand
Eleonora A. M. Festen
A.A. van Bodegraven
Gerard Dijkstra
J B A Crusius
Hein W. Verspaget
Cisca Wijmenga
Ilja M. Nolte
Rinse K. Weersma
Daan W. Hommes
Faculteit der Geneeskunde
Gastroenterology and hepatology
Pathology
Other Research
AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
CCA -Cancer Center Amsterdam
Gastroenterology and Hepatology
Gastroenterology & Hepatology
Public Health
Life Course Epidemiology (LCE)
Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Translational Immunology Groningen (TRIGR)
Groningen Institute for Organ Transplantation (GIOT)
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.

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