N01 - Age, Breed and SOD1:c.118G Genotype Related Risk of Degenerative Myelopathy: An Update

Abstract:

Background: Canine degenerative myelopathy (DM) is a debilitating condition. The DM-associated SOD1:c.118G > A genetic variant is the most common disease-associated variant in dogs. Risk of DM associated with this variant is a controversial topic.

Hypothesis/Objectives: Further characterize age- and breed-related risk for development of DM associated with the SOD1:c.118G > A variant.

Animals: Dogs with DNA voluntarily submitted for SOD1:c.118G > A variant screening were identified for follow-up, and 2,143 dogs were included following owner response.

Methods: Dogs were selected from a population screened for the SOD1:c.118G > A variant prior to age 6, who were 7 or older at follow-up. A survey was emailed to assess myelopathic signs. Responses were reviewed independent of breed, sex, or genotype, to assign dogs as having DM compatible signs or not. Kaplan-Meier survival analysis and Cox proportional hazards regression were evaluated.

Results: Cumulative event curves revealed age-related risk of disease that varies by genotype (Figure 1) and breed. Rhodesian Ridgebacks, Chesapeake Bay Retrievers, Boxers, German Shepherd Dogs, and Pembroke Welsh Corgis had sufficient numbers for analysis, and 83 breeds were represented by at least one dog. DM hazard ratio was increased over wild-type in homozygous variant and heterozygous dogs.

Conclusions and clinical importance: This study illustrates effect of SOD1:c.118G > A genotype on development of DM-compatible signs in several breeds, including increased risk in heterozygous dogs over wild-type. Agreement between clinical signs and genotype underscores use of genetic testing as an adjunctive diagnostic tool and for screening of breeding animals.