Author + information
- Amber E. Johnson,
- Karen Hanley-Yanez,
- Clyde Yancy,
- Anne Taylor,
- Arthur Feldman and
- Dennis McNamara
Background: G-protein receptor kinases (GRKs) are central to beta receptor inactivation. A polymorphism for GRK5, common in African Americans, substitutes leucine (T allele) for glutamine (A allele) at amino acid 41. GRK5 Leu41 boosts beta receptor desensitization, and may impact heart failure survival. We evaluated the impact of this polymorphism on outcomes in the African American Heart Failure Trial (A-HeFT).
Methods: A 350 patient cohort from the A-HeFT genetic sub-study, Genetic Risk Assessment of Heart Failure in African Americans (GRAHF1), was genotyped for the Gln41Leu polymorphism. Patients were followed to either death or heart failure hospitalization. Event-free survival was compared by genotype (AA homozygotes versus TT and TA subjects combined) by Kaplan Meier log rank analysis.
Results: The GRK5 genotypes observed in GRAHF1 were % AA/TA/TT= 55/38/6 with an allele frequency A=0.75 and T=0.25. The T allele was associated with decreased event-free survival overall (1 year 83% vs 77%, p-value = 0.046, Figure). The event-free survival impact was particularly evident in those not on a beta-blocker (1 year 85% vs 59%, p-value = 0.04). There was no significant difference among those on beta-blockers (82% vs 80%, p=0.19).
Conclusions: GRK5 Leu41 polymorphism was associated with decreased event-free survival in AHeFT, particularly if not on beta-blocker therapy. Further analysis of the pharmacogenomics of the interaction of genomic background and the response to heart failure therapy is required.
Moderated Poster Contributions
Heart Failure and Cardiomyopathies Moderated Poster Theater, Poster Hall, Hall C
Saturday, March 18, 2017, 12:45 p.m.-12:55 p.m.
Session Title: Put Your Codon! Genetic Insights Into Heart Failure
Abstract Category: 12. Heart Failure and Cardiomyopathies: Basic
Presentation Number: 1226M-05
- 2017 American College of Cardiology Foundation