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Updated: Mar 14, 2026

Viral Transgene Expression in Rodent Hearts and the Assessment of Cardiac Arrhythmia Risk
Published on: July 27, 2022
Genome-wide approach to identify novel candidate genes for beta blocker response in heart failure using an
David E Lanfear1, James J Yang, Sudhish Mishra
1Heart and Vascular Institute, Henry Ford Hospital, Detroit, Michigan 48202, USA.
Background:
We explored use of a canine model of heart failure (HF) for pharmacogenomic discovery, specifically analyzing response to beta blockers (BB).
Methods:
Dogs with HF that received BB (n=39) underwent genome-wide genotyping to test the association with changes in left ventricular (LV) volume and ejection fraction after treatment. Resulting candidate genes underwent RNA quantification in cardiac tissue from normal (n=5), placebo-HF (n=5), and BB-HF (n=7) dogs.
Results:
Three markers met whole-genome significance for association with improved LV end-systolic volume after BB therapy (each p<5 x 10(-7)). RNA quantification of three candidate genes near these markers -- GUCA1B, RRAGD, and MRPS10 -- revealed that gene expression levels in BB-HF dogs were between that of placebo-HF dogs and normal dogs.
Conclusion:
Genome-wide pharmacogenomic screening in a canine model of HF suggests 3 novel BB response candidate loci. This approach is adaptable to discovering mechanisms of action for other drug therapies, and may be a useful strategy for identifying candidate genes for drug response in the pre-clinical setting.
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