This study was presented in part as an oral research abstract at the 2013 ACVIM Forum, Seattle, Washington.
Identification of PDE5A:E90K: A Polymorphism in the Canine Phosphodiesterase 5A Gene Affecting Basal cGMP Concentrations of Healthy Dogs
Article first published online: 16 DEC 2013
Copyright © 2013 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 28, Issue 1, pages 78–83, January/February 2014
How to Cite
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: 78–83. doi: 10.1111/jvim.12256
- Issue published online: 15 JAN 2014
- Article first published online: 16 DEC 2013
- Manuscript Accepted: 22 OCT 2013
- Manuscript Revised: 1 SEP 2013
- Manuscript Received: 5 JUN 2013
- Individualized medicine;
- Pulmonary hypertension;
- Sildenafil citrate;
- Single nucleotide polymorphisms
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.
Functional polymorphisms exist in the canine PDE5A gene. Specific objectives were to identify PDE5A polymorphisms and evaluate their functional relevance.
Seventy healthy dogs.
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.
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.