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揭示哮喘和过敏性疾病复杂的遗传基础。

Unraveling the complex genetic underpinnings of asthma and allergic disorders.

机构信息

Department of Pediatrics, Baylor College of Medicine & Texas Children's Hospital, Texas, USA.

出版信息

Curr Opin Allergy Clin Immunol. 2010 Oct;10(5):434-42. doi: 10.1097/ACI.0b013e32833da71d.

Abstract

PURPOSE OF REVIEW

Asthma and other allergic diseases are complex genetic disorders that result from interactions between multiple genes and environmental factors. In this review, we summarize findings from candidate gene analyses, discuss the recent success of genome-wide association (GWA) studies, and outline challenges facing the field.

RECENT FINDINGS

In the past year, five GWA studies have been reported for asthma, one for atopic dermatitis, and four for intermediate phenotypes using quantitative trait loci. These results have in general been more robust to replication than prior candidate gene studies, and have allowed the identification of novel loci for both asthma (i.e. 1q31, 9q21.31) and atopic dermatitis (11q13).

SUMMARY

The integration of results from recent GWA studies with careful analyses of candidate gene associations studies has confirmed the importance of immune detection and TH2-cell mediated immune responses in the pathogenesis of allergic disease, and has raised new interest in the role of epithelial barrier function and tissue-level responses. GWA studies appear to provide a robust way to identify novel gene loci contributing to disease susceptibility. Dissecting gene-gene and gene-environment interactions, and exploring the contribution of epigenetic phenomena to allergic disease susceptibility remain important challenges to understanding the complex nature of asthma and other allergic diseases.

摘要

目的综述

哮喘和其他过敏性疾病是复杂的遗传疾病,由多个基因和环境因素相互作用所致。在这篇综述中,我们总结了候选基因分析的结果,讨论了全基因组关联(GWA)研究的最新进展,并概述了该领域面临的挑战。

最近的发现

在过去的一年中,已有五项 GWA 研究针对哮喘、一项针对特应性皮炎、四项针对使用定量性状基因座的中间表型进行了报道。这些结果总体上比之前的候选基因研究更具可重复性,并且已经确定了哮喘(即 1q31、9q21.31)和特应性皮炎(11q13)的新基因座。

总结

将最近的 GWA 研究结果与对候选基因关联研究的仔细分析相结合,证实了免疫检测和 TH2 细胞介导的免疫反应在过敏性疾病发病机制中的重要性,并引起了人们对上皮屏障功能和组织水平反应在疾病易感性中的作用的新兴趣。GWA 研究似乎为识别导致疾病易感性的新基因座提供了一种可靠的方法。剖析基因-基因和基因-环境相互作用,以及探索表观遗传现象对过敏性疾病易感性的贡献,仍然是理解哮喘和其他过敏性疾病复杂性质的重要挑战。

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