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Meta-analysis of filaggrin polymorphisms in eczema and asthma: robust risk factors in atopic disease.

Abstract

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.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Division of Environmental Dermatology and Allergy, Helmholtz Zentrum Munich and ZAUM-Center for Allergy and Environment, Technische Universität München, Munich, Germany.

    , , , , , ,

    Source

    MeSH

    Alleles
    Asthma
    Case-Control Studies
    Eczema
    Genetic Predisposition to Disease
    Genotype
    Humans
    Intermediate Filament Proteins
    Mutation
    Polymorphism, Genetic
    Risk Factors

    Pub Type(s)

    Journal Article
    Meta-Analysis
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    19501237

    Citation

    Rodríguez, Elke, et al. "Meta-analysis of Filaggrin Polymorphisms in Eczema and Asthma: Robust Risk Factors in Atopic Disease." The Journal of Allergy and Clinical Immunology, vol. 123, no. 6, 2009, pp. 1361-70.e7.
    Rodríguez E, Baurecht H, Herberich E, et al. Meta-analysis of filaggrin polymorphisms in eczema and asthma: robust risk factors in atopic disease. J Allergy Clin Immunol. 2009;123(6):1361-70.e7.
    Rodríguez, E., Baurecht, H., Herberich, E., Wagenpfeil, S., Brown, S. J., Cordell, H. J., ... Weidinger, S. (2009). Meta-analysis of filaggrin polymorphisms in eczema and asthma: robust risk factors in atopic disease. The Journal of Allergy and Clinical Immunology, 123(6), pp. 1361-70.e7. doi:10.1016/j.jaci.2009.03.036.
    Rodríguez E, et al. Meta-analysis of Filaggrin Polymorphisms in Eczema and Asthma: Robust Risk Factors in Atopic Disease. J Allergy Clin Immunol. 2009;123(6):1361-70.e7. PubMed PMID: 19501237.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Meta-analysis of filaggrin polymorphisms in eczema and asthma: robust risk factors in atopic disease. AU - Rodríguez,Elke, AU - Baurecht,Hansjörg, AU - Herberich,Esther, AU - Wagenpfeil,Stefan, AU - Brown,Sara J, AU - Cordell,Heather J, AU - Irvine,Alan D, AU - Weidinger,Stephan, PY - 2009/02/07/received PY - 2009/03/21/revised PY - 2009/03/24/accepted PY - 2009/6/9/entrez PY - 2009/6/9/pubmed PY - 2009/6/27/medline SP - 1361 EP - 70.e7 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 123 IS - 6 N2 - 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. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/19501237/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(09)00524-7 DB - PRIME DP - Unbound Medicine ER -