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

被引:4
|
作者
Castano-Amores, Celia [1 ]
Antunez-Rodriguez, Alba [2 ]
Pozo-Agundo, Ana [2 ]
Garcia-Rodriguez, Sonia [2 ]
Martinez-Gonzalez, Luis Javier [3 ]
Davila-Fajardo, Cristina Lucia [4 ]
机构
[1] Hosp Univ Santa Barbara, Pharm Dept, Puertollano, Spain
[2] Univ Granada, Ctr Genom & Oncol Res Pfizer, Genom Unit, GENYO,Andalusian Reg Govt GENYO, Granada, Spain
[3] Univ Granada, Fac Med, Dept Biochem & Mol Biol & Immunol 3, PTS, Granada, Spain
[4] Hosp Univ Virgen Nieves, Inst Invest Biosanit Granada Ibs Granada, Pharm Dept, Granada, Spain
关键词
Betablockers; Pharmacogenetic; Acute coronary syndrome; Bisoprolol; ADRB genes; BLOOD-PRESSURE RESPONSE; HEART-FAILURE; RECEPTOR POLYMORPHISMS; BETA(2)-ADRENERGIC RECEPTOR; BETA-2-ADRENERGIC RECEPTOR; ARG389GLY POLYMORPHISM; MYOCARDIAL-INFARCTION; BISOPROLOL THERAPY; GENOTYPE; PHARMACOKINETICS;
D O I
10.1016/j.biopha.2023.115869
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
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页数:9
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