Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics.
Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerife, Spain.
Curr Opin Pulm Med. 2019 Jan;25(1):101-112. doi: 10.1097/MCP.0000000000000533.
Asthma exacerbations have been suggested to result from complex interactions between genetic and nongenetic components. In this review, we provide an overview of the genetic association studies of asthma exacerbations, their main results and limitations, as well as future directions of this field.
Most studies on asthma exacerbations have been performed using a candidate-gene approach. Although few genome-wide association studies of asthma exacerbations have been conducted up to date, they have revealed promising associations but with small effect sizes. Additionally, the analysis of interactions between genetic and environmental factors has contributed to better understand of genotype-specific responses in asthma exacerbations.
Genetic association studies have allowed identifying the 17q21 locus and the ADRB2 gene as the loci most consistently associated with asthma exacerbations. Future studies should explore the full spectrum of genetic variation and will require larger sample sizes, a better representation of racial/ethnic diversity and a more precise definition of asthma exacerbations. Additionally, the analysis of important environmental gene-environment analysis and the integration of multiple omics will allow understanding the genetic factors and biological processes underlying the risk for asthma exacerbations.
哮喘加重被认为是遗传和非遗传因素之间复杂相互作用的结果。在这篇综述中,我们概述了哮喘加重的遗传关联研究,及其主要结果和局限性,以及该领域的未来方向。
大多数哮喘加重的研究都采用了候选基因的方法。尽管迄今为止已经进行了少数几项哮喘加重的全基因组关联研究,但它们揭示了有希望的关联,但效应大小较小。此外,遗传和环境因素之间相互作用的分析有助于更好地了解哮喘加重中特定基因型的反应。
遗传关联研究已经确定了 17q21 基因座和 ADRB2 基因是与哮喘加重最一致相关的基因座。未来的研究应该探索全基因组的遗传变异,并需要更大的样本量、更好地代表种族/民族多样性以及更精确地定义哮喘加重。此外,重要的环境基因-环境分析和多个组学的整合将有助于理解哮喘加重风险背后的遗传因素和生物学过程。