The impact of genomic variants on patient response to inhaled bronchodilators: a comprehensive update.

IF 3.9 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2023-01-01 DOI:10.1080/17425255.2023.2221848

Maria Gabriella Matera, Paola Rogliani, Giuseppe Novelli, Mario Cazzola

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引用次数: 0

Abstract

Introduction: The bronchodilator response (BDR) depends on many factors, including genetic ones. Numerous single nucleotide polymorphisms (SNPs) influencing BDR have been identified. However, despite several studies in this field, genetic variations are not currently being utilized to support the use of bronchodilators.

Areas covered: In this narrative review, the possible impact of genetic variants on BDR is discussed.

Expert opinion: Pharmacogenetic studies of β₂-agonists have mainly focused on ADRB2 gene. Three SNPs, A46G, C79G, and C491T, have functional significance. However, other uncommon variants may contribute to individual variability in salbutamol response. SNPs haplotypes in ADRB2 may have a role. Many variants in gene coding for muscarinic ACh receptor (mAChR) have been reported, particularly in the M₂ and, to a lesser degree, M₃ mAChRs, but no consistent evidence for a pharmacological relevance of these SNPs has been reported. Moreover, there is a link between SNPs and ethnic and/or age profiles regarding BDR. Nevertheless, replication of pharmacogenetic results is limited and often, BDR is dissociated from what is expected based on SNP identification. Pharmacogenetic studies on bronchodilators must continue. However, they must integrate data derived from a multi-omics approach with epigenetic factors that may modify BDR.

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基因组变异对患者吸入支气管扩张剂反应的影响:全面更新。

支气管扩张剂反应(BDR)取决于许多因素，包括遗传因素。已经确定了许多影响BDR的单核苷酸多态性(snp)。然而，尽管在这一领域进行了几项研究，目前还没有利用遗传变异来支持支气管扩张剂的使用。涉及领域:在这篇叙述性综述中，讨论了遗传变异对BDR的可能影响。专家意见:β2激动剂的药物遗传学研究主要集中在ADRB2基因上。A46G、C79G和C491T三个snp具有功能意义。然而，其他不常见的变异可能导致沙丁胺醇反应的个体差异。ADRB2中的snp单倍型可能起作用。据报道，毒蕈碱ACh受体(mAChR)的许多基因编码变异，特别是在M2和较小程度的M3 mAChR中，但没有一致的证据表明这些snp与药理学相关。此外，snp与BDR的种族和/或年龄谱之间存在联系。然而，药物遗传学结果的复制是有限的，而且通常，BDR与基于SNP鉴定的预期分离。支气管扩张剂的药理学研究必须继续进行。然而，他们必须将来自多组学方法的数据与可能改变BDR的表观遗传因素结合起来。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Opinion on Drug Metabolism & Toxicology 医学-生化与分子生物学

CiteScore

7.90

自引率

2.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Expert Opinion on Drug Metabolism & Toxicology (ISSN 1742-5255 [print], 1744-7607 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on all aspects of ADME-Tox. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering metabolic, pharmacokinetic and toxicological issues relating to specific drugs, drug-drug interactions, drug classes or their use in specific populations; issues relating to enzymes involved in the metabolism, disposition and excretion of drugs; techniques involved in the study of drug metabolism and toxicology; novel technologies for obtaining ADME-Tox data. Drug Evaluations reviewing the clinical, toxicological and pharmacokinetic data on a particular drug. The audience consists of scientists and managers in the pharmaceutical industry, pharmacologists, clinical toxicologists and related professionals.