title: Association between nucleotide oligomerisation domain two (Nod2) gene polymorphisms and canine inflammatory bowel disease.
abstract: The most important genetic associations that have been implicated to play a role in the etiology of Crohn's disease (CD) in humans are single nucleotide polymorphisms (SNPs) in nucleotide oligomerisation domain 2 (NOD2). The aim of this study was to investigate whether SNPs in the canine NOD2 gene are associated with inflammatory bowel disease (IBD) in German shepherd dogs (GSDs) and other canine breeds. A mutational analysis of the NOD2 gene was carried out in 10 randomly selected GSDs with IBD. The mutational analysis identified five non-synonymous SNPS, of which four in exon 3 of the NOD2 gene were evaluated in a case-control study using sequence based typing. Sequencing information from 55 GSDs with IBD were compared to a control group consisting of 61 GSDs. In addition, 85 dogs of other breeds with IBD and a breed-matched control group consisting of 162 dogs were also genotyped. All four SNPs were in complete linkage and, in the GSD population, were found to be in Hardy-Weinberg equilibrium. When the GSD case population was compared to the GSD control group, the heterozygote genotype for all four SNPs was more frequently found in the IBD population (p=0.03, OR=2.30, CI=1.07-4.94). However, these results were not mirrored in other canine breeds. Our study suggests that the four SNPs in exon 3 of NOD2 are significantly associated with IBD in GSDs when analyzed in an over-dominant model. However, these results were not mirrored in other canine breeds with IBD. This suggests that the etiology of this disease is complex and may involve the interaction of SNPs present in several genes or pathways to bring about the inflammatory changes seen in the intestine.
authors.affiliation: Department of Veterinary Clinical Sciences and Services, Royal Veterinary College, University of London, Hatfield, Hertfordshire, UK.
authors.forename: A
authors.initials: A
authors.lastname: Kathrani
authors.affiliation: Department of Veterinary Clinical Sciences and Services, Royal Veterinary College, University of London, Hatfield, Hertfordshire, UK.
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Veterinary Clinical Sciences and Services, Royal Veterinary College, University of London, Hatfield, Hertfordshire, UK.
authors.forename: C
authors.initials: C
authors.lastname: White
authors.affiliation: Department of Pathology and Infectious Diseases, Royal Veterinary College, University of London, Hatfield, Hertfordshire, UK.
authors.forename: B
authors.initials: B
authors.lastname: Catchpole
authors.affiliation: Department of Veterinary Basic Sciences, Royal Veterinary College, University of London, Hatfield, Hertfordshire, UK.
authors.forename: A
authors.initials: A
authors.lastname: Murphy
authors.affiliation: Department of Clinical Sciences, School of Veterinary Science, University of Liverpool, Liverpool, UK.
authors.forename: A
authors.initials: A
authors.lastname: German
authors.affiliation: Department of Pathology and Infectious Diseases, Royal Veterinary College, University of London, Hatfield, Hertfordshire, UK.
authors.forename: D
authors.initials: D
authors.lastname: Werling
authors.affiliation: Department of Veterinary Clinical Sciences and Services, Royal Veterinary College, University of London, Hatfield, Hertfordshire, UK. Electronic address: kallenspach@rvc.ac.uk.
authors.forename: K
authors.initials: K
authors.lastname: Allenspach
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D020022:Genetic Predisposition to Disease; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000662:veterinary*; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic
chemical_list: D053473:Nod2 Signaling Adaptor Protein
keywords: Canine; Inflammatory bowel disease; Nucleotide oligomerisation domain; Polymorphisms