1. ¹Department of Paediatric Gastroenterology, Yorkhill Hospital, Glasgow, UK
2. ²Gastrointestinal Unit, Molecular Medicine Centre, Western General Hospital, University of Edinburgh, Edinburgh, UK
3. ³Department of Child Life and Health, University of Edinburgh, Edinburgh, UK
4. ⁴Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, UK
5. ⁵Public Health Sciences, University of Edinburgh, Edinburgh, UK

Correspondence: Dr RK Russell, Department of Paediatric Gastroenterology, Yorkhill Hospital, Dalnair Street, Glasgow G3 8SJ, UK. E-mail: richardrussell@nhs.net

Received 15 January 2008; Revised 6 May 2008; Accepted 12 May 2008; Published online 19 June 2008.

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.