C08 - Association of the TTN and PDK4 Gene Variants with Dilated Cardiomyopathy in British Doberman Pinschers

Abstract:

Background: A missense mutation in the titin gene (TTN) and a splice-site mutation in the pyruvate dehydrogenase kinase 4 gene (PDK4) have been associated with dilated cardiomyopathy (DCM) in Doberman Pinchers from the US. Hypothesis: The previously reported TTN and PDK4 variants would be associated with DCM in a population of Doberman Pinchers from the United Kingdom. Animals: 84 client owned dogs (40 control dogs and 44 dogs with DCM).

Methods: Allele frequencies for each variant were calculated. Chi-square test used to assess for differences in genotype proportions between groups.

Results: Overall allele frequency in this cohort was 35% for the TTN variant and 18% for the PDK4 variant. Of the dogs with DCM, 19/44 (43%) were wild type (WT), 19/44 (43%) were heterozygous and 6/44 (14%) were homozygous for the TTN variant. In the control dogs, 19/40 (47.5%) were wild type (WT), 15/40 (37.5%) were heterozygous and 6/40 (15%) were homozygous for the TTN variant. When the PDK4 variant was sequenced, of the DCM dogs 33/44 (75%) were wild-type (WT), 5/44 (11%) were heterozygous and 6/44 (14%) were homozygous, and for the control dogs 31/40 (77.5%) were wild-type (WT), 4/40 (10%) were heterozygous and 5/40 (12.5%) were homozygous. There was no difference in the genotype frequencies for either the TTN variant (p = 0.87) or PDK4 variant (p = 0.96) between DCM dogs and control dogs. Conclusions and clinical importance: Neither the previously reported TTN variant or PDK4 appear associated with DCM in a British population of Doberman Pinchers.