title: The influence of clinical and genetic factors on left ventricular wall thickness in Ragdoll cats.
abstract: OBJECTIVE
  To investigate the effect of various genetic and environmental modifiers on left ventricular (LV) wall thickness in a cohort of cats genotyped for the myosin binding protein C3 mutation (MYBPC3).
  
  
  METHODS
  Sixty-four Ragdoll cats.
  
  
  METHODS
  All cats were screened for HCM with echocardiography and genotyping for the HCM-associated MYBPC3:R820W mutation. Cats were also genotyped for previously identified variant polymorphisms of the angiotensin-converting enzyme (ACE) and cardiac beta-adrenergic receptor (ADRB1) genes. Plasma N-terminal pro-B-type natriuretic peptide and cardiac troponin I were also measured. Associations were evaluated between genotype (MYBPC3 negative/positive, and ACE and ADRB1 negative/heterozygous/homozygous), patient factors (body weight, age and sex) and echocardiographic measurements of LV wall thickness.
  
  
  RESULTS
  Male cats had greater maximum wall thickness (LVmax; 5.8 mm, IQR 5.1-6.4 mm) than females (4.7 mm, IQR 4.4-5.3 mm, p = 0.002). Body weight positively correlated with LVmax (ρ = 0.604, p < 0.001). The MYBPC3:R820W-positive cats had a greater LVmax (5.44 mm, IQR 4.83-6.28 mm) than the negative cats (4.76 mm, IQR 4.36-5.32 mm, p = 0.001). Also, the ACE polymorphism genotype was associated with LVmax: the homozygous cats (5.37 mm, IQR 5.14-6.4 mm) had greater LVmax than the heterozygous cats (4.73 mm, IQR 4.41-5.55 mm, p = 0.014). Only the MYBPC3 genotype and body weight were independently associated with wall thickness in multivariable analysis.
  
  
  CONCLUSIONS
  This study provides evidence that the MYBPC3:R820W mutation is independently associated with LV wall thickness in Ragdoll cats. Body weight is also independently associated with maximum LV wall thickness, but is not currently accounted for in HCM screening. In addition, other genetic modifiers may be associated with variation in LV wall thickness in Ragdolls.
authors.affiliation: Royal Veterinary College, Hatfield, AL9 7TA, United Kingdom; Highcroft Veterinary Referrals, Bristol, BS14 9BE, United Kingdom. Electronic address: kieran.borgeat@highcroftvet.co.uk.
authors.forename: Kieran
authors.initials: K
authors.lastname: Borgeat
authors.affiliation: School of Veterinary Medicine, University of California Davis, Davis, CA 95616, United States.
authors.forename: Joshua
authors.initials: J
authors.lastname: Stern
authors.affiliation: North Carolina State College of Veterinary Medicine, Raleigh, NC 27607, United States.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Meurs
authors.affiliation: Royal Veterinary College, Hatfield, AL9 7TA, United Kingdom.
authors.forename: Virginia Luis
authors.initials: VL
authors.lastname: Fuentes
authors.affiliation: Royal Veterinary College, Hatfield, AL9 7TA, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Connolly
mesh_terms: D000818:Animals; D001835:Body Weight; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002415:Cats / Q000033:anatomy & histology* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006352:Heart Ventricles / Q000033:anatomy & histology*; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D012737:Sex Factors; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C
keywords: Breed screening; Cardiomyopathy; Genetics; Modifier genes