Background and importance β-Blockers are commonly prescribed to treat multiple cardiovascular (CV) diseases, but, frequently, adverse drug reactions and intolerance limit their use in clinical practice. Interindividual variability in response to β-blockers may be explained by genetic differences. In fact, pharmacogenetic interactions for some of these drugs have been widely studied, such as metoprolol. But studies that explore genetic variants affecting bisoprolol response are inconclusive, limited or confusing because of mixed results with other β-blockers, different genetic polymorphisms observed, endpoint studied, and so on.
Aim and objectives The aim of this study was to perform a systematic review in order to find relevant genetic variants affecting bisoprolol response and to perform a meta-analysis.
Material and methods Systematic review of genetic variants affecting bisoprolol. We performed a search in Pubmed on 15 January 2021 using MESH terms in the following argument: (‘Bisoprolol’ OR ‘Metoprolol’ OR ‘Adrenergic Beta antagonist’) AND (‘Pharmacogenetic’ OR ‘Single Nucleotide Polymorphism (SNP)’ OR Polymorphism’). We included ‘metoprolol’ and ‘adrenergic beta antagonist’ to detect research with combined results of various β-blockers.
We conducted a random-effects meta-analysis in recessive, dominant, codominant and overdominant models for the G risk allele in order to assess the association between ADRB1 A389G (rs1801253) and bisoprolol.
We used R statistics software, version 3.6.2, package ‘meta’ to conduct the meta-analysis (https://CRAN.R-project.org/package=meta) and Harbord′s test in order to quantitatively assess publication bias, considering a p value < 0.1 as significant statistical publication bias.
Results We found 13 publications studying the association of genetic polymorphisms with patients’ response to bisoprolol (Figure 1). Most of them focused on ADRB variants, and even though the ADRB1 Arg389Gly variant seems to have an influence on bisoprolol efficacy, the results are inconclusive and our meta-analysis did not find any statistically significant results in this regard.
Conclusion and relevance Many genetic polymorphisms have been assessed with respect to their influence on patients’ response to bisoprolol and ADRB1 Arg389Gly (rs1801253) seems the most relevant genetic polymorphism in this regard but the results have not been confirmed with a meta-analysis.
Our results support the need of further studies about the impact of genetic variants on bisoprolol response, considering different genetic polymorphisms, conducting single and multiple single nucleotide polymorphisms (SNPs) analysis, including other clinical parameters in a multivariate study.
Conflict of interest No conflict of interest
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.