Department of Human Genetics, The University of Chicago, Chicago, IL 60637, USA.
Immunol Rev. 2011 Jul;242(1):10-30. doi: 10.1111/j.1600-065X.2011.01029.x.
Asthma and allergy are common conditions with complex etiologies involving both genetic and environmental contributions. Recent genome-wide association studies (GWAS) and meta-analyses of GWAS have begun to shed light on both common and distinct pathways that contribute to asthma and allergic diseases. Associations with variation in genes encoding the epithelial cell-derived cytokines, interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP), and the IL1RL1 gene encoding the IL-33 receptor, ST2, highlight the central roles for innate immune response pathways that promote the activation and differentiation of T-helper 2 cells in the pathogenesis of both asthma and allergic diseases. In contrast, variation at the 17q21 asthma locus, encoding the ORMDL3 and GSDML genes, is specifically associated with risk for childhood onset asthma. These and other genetic findings are providing a list of well-validated asthma and allergy susceptibility genes that are expanding our understanding of the common and unique biological pathways that are dysregulated in these related conditions. Ongoing studies will continue to broaden our understanding of asthma and allergy and unravel the mechanisms for the development of these complex traits.
哮喘和过敏是常见的疾病，其病因复杂，涉及遗传和环境因素的共同作用。最近的全基因组关联研究（GWAS）和 GWAS 的荟萃分析开始揭示导致哮喘和过敏性疾病的常见和独特途径。与编码上皮细胞衍生细胞因子白细胞介素 33（IL-33）和胸腺基质淋巴细胞生成素（TSLP）的基因以及编码 IL-33 受体 ST2 的 IL1RL1 基因变异的关联，突出了先天免疫反应途径在哮喘和过敏性疾病发病机制中的核心作用，这些途径促进了辅助性 T 细胞 2 型的激活和分化。相比之下，17q21 哮喘基因座（编码 ORMDL3 和 GSDML 基因）的变异与儿童期发病的哮喘风险特异性相关。这些和其他遗传发现提供了一系列经过充分验证的哮喘和过敏易感性基因，这些基因扩展了我们对这些相关疾病中失调的常见和独特生物学途径的理解。正在进行的研究将继续拓宽我们对哮喘和过敏的理解，并揭示这些复杂特征发展的机制。
