Abstract 368: Beta-1 Adrenergic Receptor Haplotypes Based on Codon 389 and 49 Polymorphisms Influence the Magnitude of the Left Ventricular Ejection Fraction Response to Beta-blocker Therapy
Introduction Long term stimulation of the sympathetic nervous system is associated with myocardial remodeling and randomized trials have demonstrated β-blockers improve mortality and left ventricular ejection fraction (LVEF) in the HF population. Improvement of the LVEF with β-blocker therapy displays a high degree of inter-individual and inter-ethnic variation that might be explained by underlying genetic variation in adrenergic mechanisms. The β1 adrenergic receptor (AR) plays a critical role for maintenance of homeostasis in the human heart. β1 389 and 49 AR polymorphisms have been shown to act as disease modifiers in HF. A haplotype represents a certain combination of two or more polymorphism at a locus. Haplotypes are often more informative in association studies than are individual single nucleotide polymorphisms (SNPs). We hypothesized that the inter-individual variation in LVEF with β-blockers might be influenced by the different haplotypes of the β1 AR gene
Methods. 485 patients with LVEF ≤ 40% from any etiology were selected from the HF Clinic at the University of Colorado Hospital and correlation between the different β-1 AR haplotypes and LVEF response to β-blockade therapy was evaluated retrospectively.
Results With β1 AR 389 and 49 SNP, haplotype analysis demonstrated that for African Americans, the combination Gly389/Gly49 did not co-occur. There was a highly significant relationship between these 4 genetic combinations and LVEF improvement.The association between the different haplotypes and LVEF changes on β-blockade therapy are shown in Table⇓ with the P-values in parentheses. A P-value<0.05 was considered to be statistically significant. The referent in the comparisons was the Arg389/Ser49 wild-type haplotype. Conclusion This study shows a strong and significant association between the different β-1 AR haplotypes (based on codon 49 and 389 polymorphisms) and improvement in LVEF with β-blocker therapy.