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小儿哮喘的药物遗传学:当前观点

Pharmacogenetics of Pediatric Asthma: Current Perspectives.

作者信息

Perez-Garcia Javier, Espuela-Ortiz Antonio, Lorenzo-Diaz Fabian, Pino-Yanes Maria

机构信息

Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain.

Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain.

出版信息

Pharmgenomics Pers Med. 2020 Mar 18;13:89-103. doi: 10.2147/PGPM.S201276. eCollection 2020.

Abstract

Asthma is a chronic respiratory disease that affects 339 million people worldwide and has a considerable impact on the pediatric population. Asthma symptoms can be controlled by pharmacological treatment. However, some patients do not respond to therapy and continue suffering from symptoms, which impair the quality of life of patients and limit their daily activity. Genetic variation has been shown to have a role in treatment response. The aim of this review is to update the main findings described in pharmacogenetic studies of pediatric asthma published from January 1, 2018 to December 31, 2019. During this period, the response to short-acting beta-agonists and inhaled corticosteroids in childhood asthma has been evaluated by eleven candidate-gene studies, one meta-analysis of a candidate gene, and six pharmacogenomic studies. The findings have allowed validating the association of genes previously related to asthma treatment response (, and ), and identifying novel associations (, and ). However, some results are not consistent across studies, highlighting the need to conduct larger studies in diverse populations with more homogeneous definitions of treatment response. Once stronger evidence was established, genetic variants will have the potential to be applied in clinical practice as biomarkers of treatment response enhancing asthma management and improving the quality of life of asthma patients.

摘要

哮喘是一种慢性呼吸道疾病,全球有3.39亿人受其影响,对儿童群体有相当大的影响。哮喘症状可通过药物治疗得到控制。然而,一些患者对治疗无反应,症状持续存在,这损害了患者的生活质量并限制了他们的日常活动。基因变异已被证明在治疗反应中起作用。本综述的目的是更新2018年1月1日至2019年12月31日发表的儿童哮喘药物遗传学研究中描述的主要发现。在此期间,十一项候选基因研究、一项候选基因的荟萃分析以及六项药物基因组学研究评估了儿童哮喘对短效β受体激动剂和吸入性糖皮质激素的反应。这些发现已证实了先前与哮喘治疗反应相关的基因(……和……)之间的关联,并确定了新的关联(……和……)。然而,不同研究的一些结果并不一致,这突出表明需要在定义治疗反应更统一的不同人群中开展更大规模的研究。一旦建立了更有力的证据,基因变异将有可能作为治疗反应的生物标志物应用于临床实践,以加强哮喘管理并改善哮喘患者的生活质量。

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