Association between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease

• Published in: Human molecular genetics Vol. 14; no. 10; pp. 1245 - 1250
• Main Authors: McGovern, Dermot P.B., Hysi, Pirro, Ahmad, Tariq, van Heel, David A., Moffatt, Miriam F., Carey, Alisoun, Cookson, William O.C., Jewell, Derek P.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.05.2005; Oxford Publishing Limited (England)
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Child; Child, Preschool; Chromosome aberrations; Colitis, Ulcerative - genetics; Crohn Disease - genetics; Female; Fundamental and applied biological sciences. Psychology; Genetic Markers; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Humans; Infant; Inflammatory bowel disease; Inflammatory Bowel Diseases - genetics; Linkage Disequilibrium; Male; Medical genetics; Medical sciences; Middle Aged; Molecular and cellular biology; Nod1 Signaling Adaptor Protein; Polymorphism, Genetic; Sequence Deletion; Chromosomal aberration; Deletion; Insertion; Digestive diseases; Genetics; Intestinal disease; Mutation; Inflammatory disease; Polymorphism
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddi135

The identification of the role of genetic variants within NOD2 (CARD15) in Crohn's disease and ulcerative colitis susceptibility highlight the role of the innate immune system in inflammatory bowel disease (IBD) pathogenesis. NOD1 (CARD4) is located on chromosome 7p14.3, in a region of known linkage to IBD and encodes an intracellular bacterial pathogen-associated molecular pattern receptor that is closely related to NOD2. We have identified strong association between haplotypes in the terminal exons of NOD1 and IBD (multi-allelic P=0.0000003) in a panel of 556 IBD trios. The deletion allele of a complex functional NOD1 indel polymorphism (ND1+32656*1) was significantly associated with early-onset IBD (P=0.0003) in unrelated cases and controls. ND1+32656*1 was also associated with extra-intestinal manifestations of IBD (P=0.04). These findings in two independent populations provide strong evidence for a role for NOD1 variants in IBD susceptibility and reinforce the role of the innate immune system in IBD pathogenesis.