title: Identification of PDE5A:E90K: a polymorphism in the canine phosphodiesterase 5A gene affecting basal cGMP concentrations of healthy dogs.
abstract: BACKGROUND
  Cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE5A) is the target of phosphodiesterase inhibitors such as sildenafil. Polymorphisms in the PDE5A gene that may predict response to therapy with sildenafil and nitric oxide, be linked to disease progression, and aid in risk assessment have been identified in human beings. Identification of polymorphisms in PDE5A could affect the physiologic actions of PDE5A and the effects of phosphodiestrase type 5 inhibitor drugs.
  
  
  OBJECTIVE
  Functional polymorphisms exist in the canine PDE5A gene. Specific objectives were to identify PDE5A polymorphisms and evaluate their functional relevance.
  
  
  METHODS
  Seventy healthy dogs.
  
  
  METHODS
  The exonic, splice-site, 3' and 5' untranslated regions of the canine PDE5A gene were sequenced in 15 dogs and aligned with the canine reference sequence. Identified polymorphisms were evaluated in 55 additional, healthy, unrelated dogs of 20 breeds. Plasma was collected from 51 of these dogs and cGMP was measured. An unpaired t-test and one-way ANOVA with Dunnett's test of multiple comparisons were used to evaluate the effect of genotype on cGMP.
  
  
  RESULTS
  A common exonic polymorphism was identified that changed glutamic acid to lysine and resulted in significantly lower cGMP concentrations in the group with polymorphism versus the wild type group (P = .014). Additionally, 6 linked single nucleotide polymorphisms in the 3' untranslated region were identified that did not alter cGMP concentrations.
  
  
  CONCLUSIONS
  A polymorphism exists in the canine PDE5A gene that is associated with variable circulating cGMP concentrations in healthy dogs and warrants investigation in diseases such as pulmonary hypertension.
authors.affiliation: Department of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina; Department of Medicine and Epidemiology, University of California Davis School of Veterinary Medicine, Davis, California.
authors.forename: J A
authors.initials: JA
authors.lastname: Stern
authors.forename: Y
authors.initials: Y
authors.lastname: Reina-Doreste
authors.forename: L
authors.initials: L
authors.lastname: Chdid
authors.forename: K M
authors.initials: KM
authors.lastname: Meurs
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004285:Dogs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000662:veterinary; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D004247:DNA; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006152:Cyclic GMP
keywords: Individualized medicine; Pharmacogenomics; Pulmonary hypertension; Sildenafil citrate; Single nucleotide polymorphisms