Rapid CommunicationsThe contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease☆,☆☆,★
Section snippets
Patient cohorts
Family collections consisted of trios of parents with a single affected offspring or families with at least 2 affected offspring. At least 1 parent was available for genotyping in 82% of families. Patients were recruited from King's College School of Medicine, Guy's Hospital, and St Mark's Hospital (London, England), Charite University Hospital (Berlin, Germany), the Department of General Internal Medicine at the Christian-Albrechts-Universitat (Kiel, Germany), and the Academic Medical Centre
Association of mutations with CD
Sibling pairs from the British/German family cohort have previously shown evidence of linkage to the IBD1 locus on chromosome 16.22 Allelic transmission distortion for 4 SNPs (P268S, R702W, G908R, and 3020insC; see Figure 1) was assessed in this family collection using the TDT.
Discussion
In this study, a cohort of more than 1200 unrelated cases of IBD has been genotyped for 4 mutations in the coding region of the NOD2 gene to address several questions relating to its contribution to IBD susceptibility. First, we used both TDT analyses and case-control studies to assess which of the mutations are independent risk factors for CD. The P268S, R702W, and 3020insC mutations were strongly associated with CD in the TDT, whereas all 4 mutations were present at a significantly higher
Acknowledgements
The authors thank Drs. J. Lennard-Jones, A. Macpherson, J. Lee, S. Bridger, S. Hodgson, M. Hudson, and S. van Deventer for patient ascertainment and Gillian Scott, Jo Hirst, and Alison Craggs for help in obtaining samples from IBD patients and families.
References (31)
- et al.
Association between insertion mutation in NOD2 gene and Crohn's disease in German and British population
Lancet
(2001) - et al.
PedCheck: a program for identification of genotype incompatibilities in linkage analysis
Am J Hum Genet
(1998) A generalisation of the transmission/disequilibrium test for uncertain-haplotype transmission
Am J Hum Genet
(1999)- et al.
A comparison of linkage disequilibrium measures for fine-scale mapping
Genomics
(1995) - et al.
A genomewide analysis provides evidence for novel linkages in inflammatory bowel disease in a large European cohort
Am J Hum Genet
(1999) - et al.
Application and interpretation of transmission/disequilibrium tests: transmission of HLA-DQ haplotypes to unaffected siblings in 526 families with type I diabetes
Am J Hum Genet
(2000) Are rare variants responsible for susceptibility to complex diseases?
Am J Hum Genet
(2001)- et al.
Linkage heterogeneity for the IBD1 locus in Crohn's pedigrees by disease onset and severity
Gastroenterology
(2000) - et al.
Susceptibility to severe ulcerative colitis is associated with polymorphism in the central MHC gene IKBL
Gastroenterology
(2000) - et al.
The IBD2 locus shows linkage heterogeneity between ulcerative colitis and Crohn disease
Am J Hum Genet
(2000)
Crohn's disease: concordance for site and clinical type in affected family members – potential hereditary influences
Gastroenterology
Epidemiology of inflammatory bowel disease in different ethnic and religious groups: limitations and aetiological clues
Int J Colorectal Dis
Pathogenesis and immune mechanisms of chronic inflammatory bowel diseases
Am J Gastroenterol
Genetics of inflammatory bowel disease: a reappraisal
Scand J Immunol
Combined segregation and linkage analysis of inflammatory bowel disease in the IBD1 region using severity to characterise Crohn's disease and ulcerative colitis
Eur J Hum Genet
Cited by (630)
Vitamin D and antibacterial immunity
2023, Feldman and Pike's Vitamin D: Volume Two: Disease and TherapeuticsIleal and colonic Crohn's disease: Does location makes a difference in therapy efficacy?
2022, Current Research in Pharmacology and Drug DiscoveryA nod to the bond between NOD2 and mycobacteria
2023, PLoS PathogensSelected Cytokines and Metalloproteinases in Inflammatory Bowel Disease
2024, International Journal of Molecular Sciences
- ☆
Address requests for reprints to: Christopher G. Mathew, Ph.D., Division of Medical and Molecular Genetics, GKT School of Medicine, King's College London, 8th Floor Guy's Tower, Guy's Hospital, London SE1 9RT, England. e-mail: [email protected]; fax: (44) 207-955-4644.
- ☆☆
Supported in the United Kingdom by the Wellcome Trust, the Generation Trust, the TR-Golden Charitable Trust, the Kati Jacobs Appeal, Axys Pharmaceuticals Inc., and the Special Trustees of the Royal Victoria Infirmary and by an equipment grant from the Guy's and St. Thomas' Hospitals Charitable Trust. Supported in Germany by the Deutsche Forschungsgemeinschaft (For 423), a Training and Mobility of Research Network grant of the European Union (ERB-4061-PL-97-0389), a competence network “Chronisch-entzündliche Darmerkrankungen,” the German Human Genome Project, and the National Genome Research Network (all funded by the German Federal Department for Research and Education).
- ★
A.P.C. and S.A.F. contributed equally to this work.