Association analyses of novel polymorphisms in the MMP-1 promoter gene with osteoarthritis secondary to hip dysplasia in dogs

hip dysplasia (hd) is a polygenic disease characterized by joint laxity and lack of congruence leading to osteoarthritis (oa). under many pathogenic conditions including arthritis, mmp-1 synthesis is augmented. the mmp-1 gene promoter contains cytokine response elements, transcription factors ap-1 and saf-1 that are increased in oa. the objective of the present study was to identify and characterize new polymorphisms of the canine mmp-1 promoter gene and evaluate their association with oa secondary to hd in different dog breeds. based on the ncbi_006587 reference sequence, two novel polymorphisms, indel ctgccct (bp31986794) and c>t (bpsnp 31986815) substitution were selected due their position in a consensus sequence belonging to a saf-1 response element. data was uploaded in the genbank database (accession number gq475524 and gq475525). 125 dogs of different breeds were sampled and hip status was evaluated through ventrodorsal extended-hip radiographs. a chi-squared analysis was performed to test the association of the variables: breed, sex and genotype for each polymorphism with oa status (healthy and affected). no significant association (p>0.05) was found between any variable and oa secondary to hd. this study does not exclude mmp-1 as a gene responsible of oa secondary to hd in the breeds sampled because only the promoter sequence was evaluated.