Genetic polymorphisms in ADRB1, ADRB2 and CYP2D6 genes and response to beta-blockers in patients with acute coronary syndrome
Metadatos
Afficher la notice complèteAuteur
Castaño-Amores, Celia; Antúnez Rodríguez, Alba; Pozo Agundo, Ana; García Rodríguez, Sonia; Martínez González, Luis Javier; Dávila Fajardo, Cristina LucíaEditorial
Elsevier
Materia
Betablockers Pharmacogenetic CYP2D6 gene
Date
2023Referencia bibliográfica
Biomedicine & Pharmacotherapy 169 (2023) 115869 [10.1016/j.biopha.2023.115869]
Résumé
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.