Park Jong Sook, Son Ji Hye, Park Choon Sik, Chang Hun Soo
Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
Department of Interdisciplinary Program in Biomedical Science, Graduate School, Soonchunhyang University, Bucheon, Korea.
Yonsei Med J. 2019 Jan;60(1):1-9. doi: 10.3349/ymj.2019.60.1.1.
For the past three decades, a large number of genetic studies have been performed to examine genetic variants associated with asthma and its subtypes in hopes of gaining better understanding of the mechanisms underlying disease pathology and to identify genetic biomarkers predictive of disease outcomes. Various methods have been used to achieve these objectives, including linkage analysis, candidate gene polymorphism analysis, and genome-wide association studies (GWAS); however, the degree to which genetic variants contribute to asthma pathogenesis has proven to be much less significant than originally expected. Subsequent application of GWAS to well-defined phenotypes, such as occupational asthma and non-steroidal anti-inflammatory drugexacerbated respiratory diseases, has overcome some of these limitations, although with only partial success. Recently, a combinatorial analysis of single nucleotide polymorphisms (SNPs) identified by GWAS has been used to develop sets of genetic markers able to more accurately stratify asthma subtypes. In this review, we discuss the implications of the identified SNPs in diagnosis of asthma and its subtypes and the progress being made in combinatorial analysis of genetic variants.
在过去三十年中，已经进行了大量的遗传学研究，以检测与哮喘及其亚型相关的基因变异，希望能更好地理解疾病病理背后的机制，并识别出可预测疾病结局的基因生物标志物。为实现这些目标，人们采用了多种方法，包括连锁分析、候选基因多态性分析和全基因组关联研究（GWAS）；然而，事实证明基因变异对哮喘发病机制的影响程度远低于最初预期。随后将GWAS应用于明确界定的表型，如职业性哮喘和非甾体抗炎药加重的呼吸道疾病，克服了其中一些局限性，不过只是部分成功。最近，对GWAS鉴定出的单核苷酸多态性（SNP）进行组合分析，已被用于开发能够更准确地对哮喘亚型进行分层的基因标记集。在这篇综述中，我们讨论了所鉴定的SNP在哮喘及其亚型诊断中的意义，以及基因变异组合分析所取得的进展。
