Detailed assessment of NOD2/CARD15 exonic variation in inflammatory bowel disease in Scotland: implications for disease pathogenesis.
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.
Department of Paediatric Gastroenterology, Yorkhill Hospital, Glasgow, UK. richardrussell@nhs.net
R K
RK
Russell
H E
HE
Drummond
D C
DC
Wilson
N H
NH
Anderson
I D R
ID
Arnott
J E
JE
Van Limbergen
J
J
Satsangi
E R
ER
Nimmo
D000293:Adolescent; D002648:Child; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D053473:Nod2 Signaling Adaptor Protein / Q000737:chemistry / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D012606:Scotland / Q000453:epidemiology
C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein