Association between nucleotide oligomerisation domain two (Nod2) gene polymorphisms and canine inflammatory bowel disease

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.