Meta-analysis of filaggrin polymorphisms in eczema and asthma: Robust risk factors in atopic disease
Meta-analysis of filaggrin polymorphisms in eczema and asthma: Robust risk factors in atopic disease
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DOI：
10.1016/j.jaci.2009.03.036
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发表时间：
2009-06-01
影响因子：
14.2
通讯作者：
Weidinger, Stephan
中科院分区：
文献类型：
--
作者：
Rodriguez, Elke;Baurecht, Hansjoerg;Weidinger, Stephan
背景：丝聚合蛋白（FLG）无效突变作为湿疹主要危险因素的发现代表了理解这种复杂疾病的重要机制的里程碑。然而，已发表的研究表明设计和效应大小方面存在差异，并且报告了哮喘的相互矛盾的结果。 目标：我们试图提供对 FLG 效应大小的更准确估计，并在广泛和包容性湿疹诊断中更好地完善 FLG 风险概况。我们还试图提供与 FLG 无效等位基因相关的哮喘风险的更详细和结论性的估计。方法：我们对涉及 5,791 例病例、26,454 名对照受试者和 1,951 个家庭的 24 项关于 FLG 突变和湿疹的研究以及涉及 3,138 例病例、17,164 名对照受试者和 1,511 名家庭的 17 项哮喘研究进行了荟萃分析。 结果：病例对照和家庭研究均显示与湿疹有很强的相关性。病例对照研究具有异质性，而家庭研究则产生了更为同质的结果。综合分析表明，FLG 单倍体不足会强烈增加湿疹风险（比值比 [OR]，3.12；95% CI，2.57-3.79），并且与更严重和皮肤科医生诊断的疾病相关。 FLG 突变也与哮喘显着相关（OR，1.48；95% CI，1.32-1.66）。然而，尽管观察到复合表型哮喘加湿疹（OR，3.29；95% CI，2.84-3.82）的强烈影响，但在没有湿疹的情况下似乎与哮喘没有关联。结论：这项荟萃分析总结了 FLG 突变带来的高湿疹风险的有力证据，并完善了其风险概况，表明与更严重和二级护理疾病相关。 FLG 突变也是哮喘的一个重要危险因素，可能有助于确定与湿疹相关的哮喘内表型。 （过敏临床免疫杂志 2009 年；123：1361-70。）
Background: The discovery of filaggrin (FLG) null mutations as a major risk factor for eczema represents a milestone toward the understanding of an important mechanism in this complex disease. However, published studies demonstrate differences concerning design and effect size, and conflicting results for asthma have been reported.Objectives: We sought to provide a more accurate estimate of FLG effect sizes and to better refine FLG risk profiles within the broad and inclusive eczema diagnosis. We also sought to provide a more detailed and conclusive estimate of the risk for asthma associated with FLG null alleles.Methods: We performed a meta-analysis of 24 studies on FLG mutations and eczema involving 5,791 cases, 26,454 control subjects, and 1,951 families as well as 17 studies on asthma involving 3,138 cases, 17,164 control subjects, and 1,511 offspring.Results: Both case-control and family studies showed strong associations with eczema. Case-control studies were heterogeneous, whereas family studies yielded more homogeneous results. Combined analysis showed that FLG haploinsufficiency strongly increases the eczema risk (odds ratio [OR], 3.12; 95% CI, 2.57-3.79) and is associated with more severe and dermatologist-diagnosed disease. FLG mutations are also significantly associated with asthma (OR, 1.48; 95% CI, 1.32-1.66). However, although strong effects for the compound phenotype asthma plus eczema (OR, 3.29; 95% CI, 2.84-3.82) were observed, there appears to be no association with asthma in the absence of eczema.Conclusions: This meta-analysis summarizes the strong evidence for a high eczema risk conferred by FLG mutations and refines their risk profiles, suggesting an association with more severe and secondary care disease. FLG mutations are also a robust risk factor for asthma and might help define the asthma endophenotype linked with eczema. (J Allergy Clin Immunol 2009;123:1361-70.)