Genetic polymorphisms in ADRB1, ADRB2 and CYP2D6 genes and response to beta-blockers in patients with acute coronary syndrome.

Autor: Castaño-Amores C; Pharmacy Department, Hospital Universitario Santa Bárbara, Puertollano, Spain., Antúnez-Rodríguez A; GENYO, Genomics Unit, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government (GENYO), Granada, Spain., Pozo-Agundo A; GENYO, Genomics Unit, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government (GENYO), Granada, Spain., García-Rodríguez S; GENYO, Genomics Unit, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government (GENYO), Granada, Spain., Martínez-González LJ; University of Granada, Department of Biochemistry and Molecular Biology III and Immunology, Faculty of Medicine, PTS, Granada, Spain., Dávila-Fajardo CL; Pharmacy Department, Instituto de Investigación Biosanitaria de Granada (ibs.Granada), Hospital Universitario Virgen de las Nieves, Granada, Spain. Electronic address: cristinal.davila.sspa@juntadeandalucia.es.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2023 Dec 31; Vol. 169, pp. 115869. Date of Electronic Publication: 2023 Nov 10.
DOI: 10.1016/j.biopha.2023.115869
Abstrakt: Betablockers (BBs) are prescribed for ischaemia in patients with acute coronary syndrome (ACS). In Spain, bisoprolol and carvedilol are the most prescribed BBs, but patients often had to discontinue them due to adverse effects. Single nucleotide polymorphisms (SNPs) in ADRB1, ADRB2 and CYP2D6 genes have strong evidence of pharmacogenetic association with BBs in heart failure or hypertension, but the evidence in ACS is limited. Therefore, our study focuses on investigating how these genes influence the response to BBs in ACS patients. We analysed the association between SNPs in ADRB1 Gly389Arg (rs1801253) and Ser49Gly (rs1801252), ADRB2 Gly16Arg (rs1042713) and Glu27Gln (rs1042714), and CYP2D* 6 (*2- rs1080985, *4- rs3892097, *10 - rs1065852) and the occurrence of bradycardia/hypotension events during one year of follow-up. We performed an observational study and included 285 ACS-PCI-stent patients. A first analysis including patients treated with bisoprolol and a second analysis including patients treated with other BBs were performed. We found that the presence of the G allele (Glu) of the ADRB2 gene (rs1042714; Glu27Gln) conferred a protective effect against hypotension-induced by BBs; OR (CI 95%) = 0,14 (0,03-0,60), p < 0.01. The ADRB2 (rs1042713; Gly16Arg) GG genotype could also prevent hypotensive events; OR (CI 95%) = 0.49 (0.28-0.88), p = 0015. SNPs in ADRB1 and CYP2D6 * 2, CYP2D6 * 4 weren´t associated with primary events. The effect of CYP2D6 * 10 does not seem to be relevant for the response to BBs. According to our findings, SNPs in ADRB2 (rs1042713, rs1042714) could potentially affect the response and tolerance to BBs in ACS-patients. Further studies are necessary to clarify the impact of ADRB2 polymorphisms.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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