The burden of disease associated with filaggrin mutations: A population-based, longitudinal birth cohort study
The burden of disease associated with filaggrin mutations: A population-based, longitudinal birth cohort study
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DOI：
10.1016/j.jaci.2008.01.026
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发表时间：
2008-04-01
影响因子：
14.2
通讯作者：
Irvine, Alan D.
中科院分区：
文献类型：
--
作者：
Henderson, John;Northstone, Kate;Irvine, Alan D.
背景：特应性疾病是一个主要的健康问题。聚丝蛋白基因（FLG）的突变赋予湿疹和相关哮喘的主要易感性。目的：我们试图在一项大型的、基于人群的出生队列研究中确定由2种最常见的FLG突变赋予的特应性疾病的自然史和负担。方法：我们分析了最常见的无效等位基因（R501 X和2282 del 4）与几种特应性表型的关系。结果：FLG无效等位基因与湿疹密切相关;与这些突变相关的湿疹出现在生命早期，并且更持久（FLG突变与FLG野生型的湿疹消退风险比为0.67; 95% CI为0.58-0.77; P = 5 x 10（-8））。FLG基因突变导致人群哮喘风险为1.80（95%CI，1.34-2.41; P = .00019）;湿疹患者的哮喘风险尤其高（比值比，3.16; 95%CI，2.25-4.43; P = 1.4 x 10（-11））。对草、屋尘螨和猫皮屑的致敏性和对多种过敏原的致敏性有很强的相关性（优势比，2.12; 95%CI，1.03-4.37; P = 5.42 x 10（-27））。结论：FLG突变是湿疹、早期喘息、湿疹背景下哮喘和特应性致敏的强遗传决定因素。它们赋予湿疹特定轨迹的风险，疾病持续时间增加，哮喘和多种过敏性致敏的风险更大。FLG等位基因有助于确定湿疹儿童的风险特征，并有助于确定“湿疹加早期喘息”和“湿疹加哮喘”表型。
Background: Atopic disease is a major health problem. Mutations in the filaggrin gene (FLG) confer major susceptibility to eczema and related asthma.Objective: We sought to determine the natural history and burden of atopic disease conferred by the 2 most common FLG mutations in a large, population-based birth cohort study.Methods: We analyzed the effect of the most common null alleles (R501X and 2282del4) on several atopic phenotypes in a cohort of approximately 7000 English children born in 1990-1991.Results: FLG null alleles associated strongly with eczema; eczema associated with these mutations presents in early life and is more persistent (hazard ratio for eczema resolution for those with FLG mutations to FLG wild type, 0.67; 95% CI, 0.58-0.77; P = 5 x 10(-8)). FLG mutations conferred a population asthma risk of 1.80 (95% CI, 1.34-2.41; P = .00019); asthma risk was especially high in the context of eczema (odds ratio, 3.16; 95% CI, 2.25-4.43; P = 1.4 x 10(-11)). Strong associations were identified with sensitization to grass, house dust mite, and cat dander and sensitization to multiple allergens (odds ratio, 2.12; 95% CI, 1.03-4.37; P = 5.42 x 10(-27)).Conclusion: FLG mutations are strong genetic determinants of eczema, early wheeze, asthma in the context of eczema, and atopic sensitization. They confer risk of a particular trajectory for eczema, with increased duration of disease and greater risk of asthma and multiple allergic sensitizations. FLG alleles help define the risk profile of children with eczema and help define the "eczema plus early wheeze" and "eczema plus asthma" phenotypes.