Identification of PDE5A:E90K: a polymorphism in the canine phosphodiesterase 5a gene affecting basal cGMP concentrations of healthy dogs

Stern, J. A., Reina-Doreste, Y., Chdid, L. and Meurs, K. M. (2014) Identification of PDE5A:E90K: a polymorphism in the canine phosphodiesterase 5a gene affecting basal cGMP concentrations of healthy dogs. Journal of Veterinary Internal Medicine, 28(1), pp. 78-83. (doi: 10.1111/jvim.12256) (PMID:24341639) (PMCID:PMC4895552)

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. Hypothesis/Objective: Functional polymorphisms exist in the canine PDE5A gene. Specific objectives were to identify PDE5A polymorphisms and evaluate their functional relevance. Animals: 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 and Clinical Importance: 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Reina Doreste, Mr Yamir
• Authors: Stern, J. A., Reina-Doreste, Y., Chdid, L., and Meurs, K. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Journal of Veterinary Internal Medicine
• Publisher: American College of Veterinary Internal Medicine.
• ISSN: 0891-6640
• ISSN (Online): 1939-1676
• Published Online: 16 December 2013