Identification of variants of the SPINK1 gene and their association with pancreatitis in Miniature Schnauzers

Objective To evaluate the serine protease inhibitor, Kazal type 1 (SPINK1) gene for variants and to determine their possible association with pancreatitis in Miniature Schnauzers. Animals-39 Miniature Schnauzers with pancreatitis, 25 healthy Miniature Schnauzers, and 23 healthy dogs of other breeds. Procedures-The entire canine SPINK1 gene with its intron-exon boundaries was initially sequenced in 22 Miniature Schnauzers. Then, 2 regions of the gene were sequenced in 65 additional canine DNA samples at the locations of variants identified in the initial sequencing of the entire SPINK1 gene. Results-Analysis of the SPINK1 gene in Miniature Schnauzers revealed 3 closely associated variants in healthy Miniature Schnauzers and Miniature Schnauzers with pancreatitis. These variants consisted of 2 missense mutations in the second exon (N20K and N25T) and a poly T insertion in the third intron that was near the boundary of exon 3 (IVS3+26-27ins(T)33-39,15_61dup11). Pancreatitis was significantly associated with homozygous alleles for these 3 variants in Miniature Schnauzers. In healthy dogs of other breeds, only the 2 exon variants were identified. Conclusions and Clinical Relevance-Variants of the SPINK1 gene may be associated with the development of pancreatitis in Miniature Schnauzers. (Am J Vet Res 2010;71:527-533)