Genetic polymorphisms in ADRB2 and ADRB1 are associated with differential survival in heart failure patients taking β-blockers

IF 2.9 3区医学 Q2 GENETICS & HEREDITY

Pharmacogenomics Journal Pub Date : 2021-10-12 DOI:10.1038/s41397-021-00257-1

Leonardo A. Guerra, Christelle Lteif, Meghan J. Arwood, Caitrin W. McDonough, Leanne Dumeny, Ankit A. Desai, Larisa H. Cavallari, Julio D. Duarte

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引用次数: 1

Abstract

Single nucleotide polymorphisms (SNPs) have been associated with differential beta-blocker (BB) effects on heart rate, blood pressure, and left ventricular ejection fraction in various patient populations. This study aimed to determine if SNPs previously associated with BB response are also associated with differential survival in heart failure (HF) patients receiving BBs. HF patient data were derived from electronic health records and the Social Security Death Index. Associations and interactions between BB dose, SNP genotype, and the outcome of death were assessed using a Cox proportional-hazard model adjusting for covariates known to be associated with differential survival in HF patients. Two SNPs, ADRB1 Arg389Gly and ADRB2 Glu27Gln, displayed significant interactions (Pint = 0.043 and Pint = 0.017, respectively) with BB dose and their association with mortality. Our study suggests that ADRB2 27Glu and ADRB1 389Arg may confer a larger survival benefit with higher BB doses in patients with HF.

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ADRB2 和 ADRB1 的基因多态性与服用 β 受体阻滞剂的心力衰竭患者的不同存活率有关

在不同的患者群体中，单核苷酸多态性（SNPs）与β-受体阻滞剂（BB）对心率、血压和左心室射血分数的不同影响有关。本研究旨在确定以前与β-受体阻滞剂反应相关的 SNPs 是否也与接受β-受体阻滞剂治疗的心力衰竭（HF）患者的不同存活率有关。心衰患者的数据来自电子健康记录和社会保障死亡指数。使用Cox比例危险模型评估了BB剂量、SNP基因型和死亡结果之间的关联和相互作用，并调整了已知与HF患者不同生存率相关的协变量。ADRB1的Arg389Gly和ADRB2的Glu27Gln这两个SNP与BB剂量及其与死亡率的关系有显著的相互作用（Pint = 0.043和Pint = 0.017）。我们的研究表明，ADRB2 27Glu 和 ADRB1 389Arg 可使高血压患者在较高的 BB 剂量下获得更大的生存获益。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenomics Journal 医学-药学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The Pharmacogenomics Journal is a print and electronic journal, which is dedicated to the rapid publication of original research on pharmacogenomics and its clinical applications. Key areas of coverage include: Personalized medicine Effects of genetic variability on drug toxicity and efficacy Identification and functional characterization of polymorphisms relevant to drug action Pharmacodynamic and pharmacokinetic variations and drug efficacy Integration of new developments in the genome project and proteomics into clinical medicine, pharmacology, and therapeutics Clinical applications of genomic science Identification of novel genomic targets for drug development Potential benefits of pharmacogenomics.