Impact of Genetic Variation in Adrenergic Receptors on β-Blocker Effectiveness and Safety in Cardiovascular Disease Management: A Systematic Review

Abstract

Background/Objectives: A systematic review was conducted to compile all the evidence on the impact of ADRB1 and ADRB2 genetic variants on the response to β-blockers, used for the management of cardiovascular diseases. Methods: After searching in PubMed, PharmGKB, and the Cochrane Central Register of Controlled Trials including terms related to these drugs, genes, and pathologies, 1182 articles were retrieved, 29 of which met the inclusion criteria. A β-adrenoreceptor (ADRB) blockade qualitative variable was inferred for all the associations between genetic variants and clinical phenotypes. Results: The relationship between ADRB1 rs1801253 (G>C) C allele and higher receptor blockade showed a moderate overall level of evidence, reaching a high level on its relationship with higher reduction in the systolic (SBP) and diastolic blood pressure and heart rate (HR). The relationship between ADRB1 rs1801252 (A>G) G allele and lower receptor blockade reached an overall high level of evidence, considering its impact on the reduction in the SBP, HR, left ventricular end-diastolic diameter, and incidence of major cardiovascular events. The relationship between ADRB2 rs1042714 (G>C) C allele and lower receptor blockade reached a moderate overall level of evidence due to its impact on HR, pulmonary wedge pressure, and left ventricular ejection fraction response. The ADRB2 rs1042713 (G>A) A allele was associated with higher receptor blockade and higher HR reduction with a low level of evidence. Conclusions: The genotyping of both ADRB1 variants may be clinically useful; further investigation is required on the relevance of both ADRB2 variants. Further research is warranted to determine the clinical usefulness of ADRB preemptive genotyping.

Keywords

• β-blocker
• adrenergic receptors
• <i>ADRB1</i>
• <i>ADRB2</i>
• genetic variant
• blockade