Tamari Mayumi, Hirota Tomomitsu
Laboratory for Respiratory Diseases, Center for Genomic Medicine, Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan..
Laboratory for Respiratory Diseases, Center for Genomic Medicine, Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
Allergol Int. 2013;62(1):21-28. doi: 10.2332/allergolint.13-RAI-0539. Epub 2015 Feb 27.
Allergic diseases are complex diseases caused by a combination of genetic and environmental factors. To determine the genetic components of these diseases and to discover the genes and cellular pathways underlying them, a large number of genetic studies have been conducted. Progress in genetics enables us to conduct genome-wide association studies (GWASs), which is a comprehensive and unbiased approach to identify susceptibility loci for multifactorial diseases. Recent GWASs have convincingly detected a large number of loci associated with allergic diseases. Candidate genes in the susceptibility loci suggest roles for epithelial barrier functions, innate-adaptive immunity, IL-1 family signaling, regulatory T cells and the vitamin D pathway in the pathogenesis of allergic diseases. Interestingly, the IL1RL1, HLA, IL13 and C11orf30 regions are overlapping susceptibility loci among atopic dermatitis and asthma or allergic rhinitis. Although a more complete collection of associated genes and pathways is needed, biologic insights revealed by GWASs improve our understanding of the pathophysiology of human allergic diseases and contribute to the development of better treatment and preventive strategies.
过敏性疾病是由遗传和环境因素共同作用引起的复杂疾病。为了确定这些疾病的遗传成分，并发现其潜在的基因和细胞途径，已经开展了大量的遗传学研究。遗传学的进展使我们能够进行全基因组关联研究（GWAS），这是一种全面且无偏倚的方法，用于识别多因素疾病的易感基因座。最近的GWAS已经令人信服地检测到大量与过敏性疾病相关的基因座。易感基因座中的候选基因表明上皮屏障功能、天然-适应性免疫、IL-1家族信号传导、调节性T细胞和维生素D途径在过敏性疾病发病机制中的作用。有趣的是，IL1RL1、HLA、IL13和C11orf30区域是特应性皮炎与哮喘或过敏性鼻炎之间重叠的易感基因座。尽管需要更完整地收集相关基因和途径，但GWAS揭示的生物学见解增进了我们对人类过敏性疾病病理生理学的理解，并有助于制定更好的治疗和预防策略。
