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Detailed assessment of NOD2/CARD15 exonic variation in inflammatory bowel disease in Scotland: implications for disease pathogenesis

Genes & Immunity volume 9, pages 556–560 (2008)Cite this article

Abstract

The high incidence of Scottish Crohn's disease (CD) is not explained by the common three NOD2/CARD15 variants. We aimed to identify population-specific NOD2/CARD15 coding variants. A total of 1478 (320 inflammatory bowel disease patients <16 years, 343 adult CD patients, 542 parents and 273 controls). All NOD2/CARD15 exons were sequenced in 24 CD patients. Sequencing identified 18 single-nucleotide polymorphisms (SNPs) including 4 non-synonymous coding SNPs altering the structure of the Leucine-rich region—two were well established (1007-/C and 908G/R). Two other variants, valine955isoleucine (955V/I) and methionine863valine (863M/V), were genotyped in all subjects. 863M/V carriage was not significantly higher in CD patients vs controls (1.35 vs 0.37%, P=0.27). 955V/I carriage was no higher in CD or ulcerative colitis patients (12.8 and 15.8%, respectively) compared to controls (16.2%). Transmission disequilibrium test analysis was negative. 955V/I carriage was higher in indeterminate colitis patients (n=29) compared to controls (41.4 vs 16.2%, P=0.001, OR=3.6 (1.6–8.2)). Population-specific NOD2/CARD15 exonic variants do not account for the high-CD prevalence in Scotland.

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Acknowledgements

We acknowledge the contribution of staff at the Medical Research Council Human Genetics Unit Edinburgh (Technical Services Department), the Wellcome Trust Clinical Research Facility Edinburgh and the referring physicians from Scottish Gastrointestinal Medicine and Surgery services.

We also acknowledge the help of all patients and parents who participated in the study together with the specialist nurses, dieticians and secretaries in each of the Scottish paediatric teaching hospitals as well as the paediatricians, practice nurses and GPs throughout Scotland whose support was invaluable. Richard K Russell was funded by a University of Edinburgh Medical Faculty Fellowship. Johan Van Limbergen is funded by a Research Training Fellowship from Action Medical Research, The Gay-Ramsay-Steel-Maitland or Stafford Trust and the Hazel M Wood Charitable Trust. Elaine R Nimmo is supported by a Wellcome Trust Programme Grant (072789/Z/03/Z). Financial assistance was also provided by Schering-Plough and the GI/Nutrition Research Fund, Child Life and Health, University of Edinburgh.

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Authors and Affiliations

  1. Department of Paediatric Gastroenterology, Yorkhill Hospital, Glasgow, UK

    R K Russell

  2. Gastrointestinal Unit, Molecular Medicine Centre, Western General Hospital, University of Edinburgh, Edinburgh, UK

    H E Drummond, I D R Arnott, J E Van Limbergen, J Satsangi & E R Nimmo

  3. Department of Child Life and Health, University of Edinburgh, Edinburgh, UK

    D C Wilson

  4. Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, UK

    D C Wilson

  5. Public Health Sciences, University of Edinburgh, Edinburgh, UK

    N H Anderson

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Russell, R., Drummond, H., Wilson, D. et al. Detailed assessment of NOD2/CARD15 exonic variation in inflammatory bowel disease in Scotland: implications for disease pathogenesis. Genes Immun 9, 556–560 (2008). https://doi.org/10.1038/gene.2008.44

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