Abstract 19037: Impact of the GNB3 C825T Polymorphism on Heart Failure Survival
Introduction: Genetic background can influence heart failure survival and the impact of therapeutics. A polymorphism of a G protein beta subunit, GNB3 C825T, has been investigated extensively for its impact on the genomic risk of hypertension. The T allele is associated with low renin hypertension and increased alpha adrenergic tone. The T allele is more prevalant in African Americans and in the AHeFT trial was associated with a greater impact of therapy with a fixed dose combination of hydralazine and isosorbide dinitrates. We investigated the impact of GNB3 C825T on transplant free survival in systolic heart failure in GRACE (Genetic Risk Assessment of Cardiac Events), a singe center study based in an outpatient heart failure clinic.
Methods: 944 subjects with systolic heart failure were enrolled from the Heart Failure Clinic at the University of Pittsburgh and followed for up to 5 years to an endpoint of death or cardiac transplantation. Demographic information was recorded at the time of enrollment and medical therapy reassessed annually. Blood was obtained at entry for DNA banking, and the GNB3 C825T genotype was determined. Transplant free survival was compared by Kaplan Meier log rank assessment.
Results: The cohort was 28% female, 13% black, 48% ischemic, mean age 56+9, mean LVEF 0.25+0.09, and was NYHA class % 1/2/3/4=4%/52%/40%/4%. In terms of the GNB3 genotype the %TT/TC/CC were 16.5%/41.8%/41.7% and the frequency of the T allele differed significantly by race and was more common in Blacks (p<0.001) . During follow up there were 236 (25%) death, and 126 transplants (13%). The T allele was associated with poor transplant free survival (Figure: p=0.025) driven primarily by poorer absolute survival (p=0.017).
Conclusions: The GNB3 825T allele was associated with poorer survival in a cohort with chronic heart failure. Its role in racial differences in heart failure outcomes warrants futher investigation.
Author Disclosures: D.M. McNamara: Research Grant; Modest; Arbor Pharmaceutical. Consultant/Advisory Board; Modest; Sanofi Pasteur, GE healthcare. Research Grant; Significant; modest. Consultant/Advisory Board; Significant; modest, modest. K. Hanley-Yanez: None. I. Halder: None. R. Sheppard: None.
- © 2015 by American Heart Association, Inc.