Chronic valvular heart disease is common in the Cavalier King Charles Spaniel (CKCS). However, genetic factors contributing to development or progression of the disease are unknown. Although classically considered a non-inflammatory disease, upregulated expression of genes involved in inflammation and immune function has been identified in affected valvular tissue. Therefore, genetic determinants of the immune response could influence disease progression in individual dogs.

The aims of this study were to document major histocompatibility haplotype (MHC) dog leukocyte antigen (DLA) class II haplotypes in the CKCS, and to examine potential associations between individual haplotypes and progression of disease.

DLA three-locus haplotypes were determined in 190 CKCS from the UK (n=95) and Australia (n=95) using sequence-based typing methods. Six haplotypes were identified.

Echocardiography was performed in 187 dogs; 72 had evidence of remodelling and 115 did not. Three dogs were not tested. Remodelling was defined as increased left-atrial-to-aortic ratio (>1.5) or increased left ventricular internal diameter during diastole or systole (normalised to bodyweight) (LVIDDi>1.85 or LVIDSi>1.26). Associations between individual haplotypes and the presence of remodelling were investigated using the Fisher's exact test. Odds ratios (OR) and 95% confidence intervals (CI) were also calculated. The age of the dogs ranged from 0.6–16.3 years.

When data from all 187 dogs were considered, two haplotypes (DRB1*01101/DQA1*00201/DQB1*01303 and DRB1*02001/DQA1*00401/DQB1*01303) were significantly associated with the presence of remodelling (p=0.0239 and p=0.0357; OR 3.562 [95% CI 1.188–10.68] and 0.5181 [0.2831–0.9482], respectively).

Echocardiographic evidence of remodelling was present in 24 dogs <9 years old and absent in 37 dogs >/=9 years old. DRB1*01101/DQA1*00201/DQB1*01303 was significantly (p=0.035) associated with the presence of remodelling at a younger age (odds ratio 3.562, [1.188–10.68]).

These results suggest an association between MHC DLA haplotype and the progression of chronic valvular heart disease in the CKCS. Further studies are recommended to explore the potential role of the immune system in the pathogenesis of this disease.

Disclosures

No disclosures to report.