New variants in ACE gene region in 10 Cavalier King Charles Spaniel dogs with mild and severe myxomatous mitral valve disease - preliminary study.
This study found no strong genetic associations between angiotensin-converting enzyme variants and the severity of myxomatous mitral valve disease in Cavalier King Charles Spaniels.
Where it sits
this study against the rest of the melanotan 1 corpusSummary and findings
This study characterized angiotensin-converting enzyme gene variation in 10 Cavalier King Charles Spaniel dogs diagnosed with myxomatous mitral valve disease. The dogs were classified into mild and severe groups according to established veterinary guidelines. The study aimed to investigate the association of genetic variants with disease severity.
Abstract
Myxomatous mitral valve disease is the most common acquired cardiac disorder in dogs, with particularly high prevalence and early onset in Cavalier King Charles Spaniels. Activation of the renin-angiotensin-aldosterone system plays a key role in disease progression, and genetic variation in the angiotensin-converting enzyme gene may influence disease severity and therapeutic response. The aim of this study was to characterize angiotensin-converting enzyme gene variation in a Polish Cavalier King Charles Spaniel population with mild and severe myxomatous mitral valve disease using targeted next-generation sequencing, with emphasis on the rs850683722 polymorphism. Ten client-owned dogs diagnosed with myxomatous mitral valve disease were prospectively enrolled and classified according to American College of Veterinary Internal Medicine guidelines into mild (stage B1) and severe (stage C/D) groups. Dogs with comorbidities or receiving medications affecting the renin-angiotensin-aldosterone system were excluded. Genomic DNA isolated from peripheral blood underwent next-generation sequencing to cover coding exons and adjacent intronic regions of the angiotensin-converting enzyme gene. Variant detection and annotation were performed using standard bioinformatic methods. A total of 188 variants were identified, of which 95,2 % were intronic. Coding variants were rare and included one missense substitution, one in-frame insertion, and three synonymous changes. Fourteen variants were novel. The rs850683722 polymorphism was present in both groups without clear association with disease stage. No variant showed a strong relationship with disease severity. Overall, angiotensin-converting enzyme gene variation was dominated by non-coding polymorphisms with potential regulatory effects, suggesting a modifying rather than causative role in disease progression.
Background
Myxomatous mitral valve disease is prevalent in Cavalier King Charles Spaniels, and the renin-angiotensin-aldosterone system is implicated in its progression. Previous studies have suggested that genetic variations in the angiotensin-converting enzyme gene may influence disease severity and treatment responses. This study seeks to explore these genetic variations in a specific population of dogs to better understand their potential role in the disease.
Methods
This study enrolled 10 client-owned Cavalier King Charles Spaniel dogs diagnosed with myxomatous mitral valve disease. The dogs were classified into mild (stage B1) and severe (stage C/D) groups based on American College of Veterinary Internal Medicine guidelines. Genomic DNA was isolated from peripheral blood and underwent next-generation sequencing to analyze coding exons and adjacent intronic regions of the angiotensin-converting enzyme gene.
Results
A total of 188 variants were identified, with 95.2% classified as intronic. Among the coding variants, one missense substitution, one in-frame insertion, and three synonymous changes were noted. The rs850683722 polymorphism appeared in both mild and severe groups without a clear association with disease stage. No variant demonstrated a strong relationship with disease severity.
Interpretation
The findings indicate that angiotensin-converting enzyme gene variation in this population is predominantly non-coding, suggesting a potential regulatory role rather than a direct causative effect on disease progression. This contrasts with prior literature that may have suggested stronger associations. The small sample size and lack of significant findings limit the conclusions that can be drawn, indicating the need for further research.
Key findings
- 188 variants identified, 95.2% were intronic.
- One missense substitution, one in-frame insertion, and three synonymous changes were found.
- Fourteen variants were novel.
- The rs850683722 polymorphism was present in both groups without clear association with disease stage.
- No variant showed a strong relationship with disease severity.
Limitations
- Small sample size of n=10 limits generalizability.
- No strong associations between variants and disease severity were found.
- Exclusion of dogs with comorbidities may affect results.
- Study focused on a specific breed, limiting broader applicability.