Genetic Association of the A31P and A74T Polymorphism in the MYBPC3 Gene and Hypertrophic Cardiomyopathy in Maine Coon Cats
ACVIM 2008
G. Wess; C. Schinner; K. Weber; K. Hartmann
Clinic for Small Animal Internal Medicine, LMU University of Munich

Hypertrophic cardiomyopathy (HCM) is the most common feline cardiac disease and is inherited as an autosomal dominant trait. The A31P and A74T single nucleotide polymorphisms (SNPs) in the MYBPC3 gene are thought to be causative mutations in Maine Coon cats. However, in many investigators' experience phenotypes often differ from genotypes. Echocardiographically confirmed HCM positive Maine coon cats may have negative genetic test results, and vice-versa. Veterinarians are therefore often unsure which recommendations they should give breeders with various test results. The aim of this study was to evaluate the association of the A31P and A74T SNPs and HCM in Maine Coon cats and to validate the clinical use of both genetic tests. The presence of these SNPs in other breeds was assessed as well.

Eighty three Maine Coon cats (mean age 71.3 month) and 68 cats of other breeds (mean age 102.4 month) were prospectively phenotyped using echocardiography as phenotype-healthy or phenotype-HCM. Inclusion criteria were a minimum age of 24 months for males and 36 months for females. The HCM-phenotype was defined as a left ventricular wall thickness of more than 6 mm in diastole measured in a 2D image using a VIVID 7 (General Electrics). Cats with hyperthyroidism or hypertension were excluded. Taqman® genotyping assays were used for genotyping. The potential impact of the SNPs was assessed with PolyPhen software.

Of the 83 Maine Coon cats 21.7% were positive and 78.3% negative for A31P. None of the other breeds had a positive A31P SNP. From the genotype-positive cats, 83.3% were phenotype-healthy and 16.7% were phenotype-HCM. From the genotype-negative cats, 86.1% were considered as phenotype-healthy and 13.9% as phenotype-HCM. 79 Maine coons were tested for the A74T SNP and 35.4% were genotype-positive. The A74T SNP was present in other breeds as well. 78.6% of the Maine Coon genotype A74T SNP positive cats had a normal ultrasound examination. The genotype-negative cats were considered as phenotype healthy in 88.2% and as HCM in 11.8%.

There was no significant allele frequency difference between HCM and healthy cats for both SNPs. Echocardiographic HCM positive cats were genotype-negative in 75% concerning the A31P and in 50% concerning the A74T SNP. None of the genetic tests could provide a useful predictive value of disease outcome. Computer based protein analysis of the evaluated SNPs indicated the potential impact of both SNPs to be "benign". The use of presently available genetic tests for selective breeding appears to be questionable according to these study results. The gold standard for the diagnosis of HCM remains the annually echocardiographic examination.

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Gerhard Wess

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