Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA.
Department of Biological Chemistry and Pharmacology, Ohio State University College of Medicine, Columbus, OH, USA.
J Cardiovasc Transl Res. 2019 Aug;12(4):280-289. doi: 10.1007/s12265-019-09866-5. Epub 2019 Feb 12.
Two common genetic polymorphisms in the beta-1 adrenergic receptor (ADRB1 Ser49Gly [rs1801252] and Arg389Gly [rs1801253]) significantly affect receptor function in vitro. The objective of this study was to determine whether ADRB1 Ser49Gly and Arg389Gly are associated with recovery of left ventricular ejection fraction (LVEF) in patients with heart failure. Patients with heart failure and baseline LVEF ≤ 40% were genotyped (n = 98), and retrospective chart review assessed the primary outcome of LVEF recovery to ≥ 40%. Un/adjusted logistic regression models revealed that Ser49Gly, but not Arg389Gly, was significantly associated with LVEF recovery in a dominant genetic model. The adjusted odds ratio for Ser49 was 8.2 (95% CI = 2.1-32.9; p = 0.003), and it was the strongest predictor of LVEF recovery among multiple clinical variables. In conclusion, patients with heart failure and reduced ejection fraction that are homozygous for ADRB1 Ser49 were significantly more likely to experience LVEF recovery than Gly49 carriers.
β1 肾上腺素能受体（ADRB1 Ser49Gly [rs1801252] 和 Arg389Gly [rs1801253]）中的两个常见遗传多态性显著影响体外受体功能。本研究的目的是确定 ADRB1 Ser49Gly 和 Arg389Gly 是否与心力衰竭患者左心室射血分数（LVEF）的恢复相关。对基线 LVEF ≤ 40%的心力衰竭患者进行基因分型（n = 98），并回顾性图表评估 LVEF 恢复至 ≥ 40%的主要结局。未调整和调整后的逻辑回归模型显示，在显性遗传模型中，Ser49Gly 而非 Arg389Gly 与 LVEF 恢复显著相关。Ser49 的调整比值比为 8.2（95%CI = 2.1-32.9；p = 0.003），并且是多个临床变量中预测 LVEF 恢复的最强因素。总之，与 Gly49 携带者相比，ADRB1 Ser49 纯合子的心力衰竭和射血分数降低的患者更有可能经历 LVEF 恢复。
