Genetic Determinants of Poor Response to Treatment in Severe Asthma.
Genetic Determinants of Poor Response to Treatment in Severe Asthma.
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DOI：
10.3390/ijms22084251
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发表时间：
2021-04-20
影响因子：
5.6
通讯作者：
Cruz AA
中科院分区：
文献类型：
--
作者：
Figueiredo RG;Costa RS;Figueiredo CA;Cruz AA
重症哮喘是一种多因素疾病，具有显著的表型异质性和遗传和环境风险因素之间复杂的相互作用，这至少部分解释了为什么在标准药物治疗期间，许多患者仍然控制不佳，并面临呼吸道重塑和疾病进展的风险增加。为了更好地适应个人独特的需求，精准医学的概念是慢性呼吸系统疾病管理的一个新兴趋势。在过去的几年里，全基因组联合研究(GWAS)揭示了与吸入皮质类固醇的反应和支气管扩张剂的临床疗效相关的新的药物遗传变体。由于遗传差异，对治疗的最佳临床反应可能因种族/民族群体或个人而异。表观遗传因素在基因表达模式和炎性细胞因子的调节中发挥关键作用，这一假设也是可信的。值得注意的是，与治疗效果相关的特定基因变异可能为重症哮喘的新治疗指明了有希望的途径。在这篇综述中，我们简要介绍了重症哮喘治疗反应差的遗传决定因素的最新进展以及该领域的未来发展方向。
Severe asthma is a multifactorial disorder with marked phenotypic heterogeneity and complex interactions between genetics and environmental risk factors, which could, at least in part, explain why during standard pharmacologic treatment, many patients remain poorly controlled and at an increased risk of airway remodeling and disease progression. The concept of “precision medicine” to better suit individual unique needs is an emerging trend in the management of chronic respiratory diseases. Over the past few years, Genome-Wide Association Studies (GWAS) have revealed novel pharmacogenetic variants related to responses to inhaled corticosteroids and the clinical efficacy of bronchodilators. Optimal clinical response to treatment may vary between racial/ethnic groups or individuals due to genetic differences. It is also plausible to assume that epigenetic factors play a key role in the modulation of gene expression patterns and inflammatory cytokines. Remarkably, specific genetic variants related to treatment effectiveness may indicate promising pathways for novel therapies in severe asthma. In this review, we provide a concise update of genetic determinants of poor response to treatment in severe asthma and future directions in the field.
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