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Rodriguez, E. ; Baurecht, H. ; Herberich, E.* ; Wagenpfeil, S.* ; Brown, S.J.* ; Cordell, H.J.* ; Irvine, A.D.* ; Weidinger, S.

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

J. Allergy Clin. Immunol. 123, 1361-1370 (2009)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Atopic eczema; atopic dermatitis; eczema; asthma; filaggrin; meta-analysis; of-function mutations; confer susceptibility; early-onset; ichthyosis vulgaris; function variants; gene predispose; null mutations; rare mutations; dermatitis; association
Sprache englisch
Veröffentlichungsjahr 2009
HGF-Berichtsjahr 2009
ISSN (print) / ISBN 0091-6749
e-ISSN 1097-6825
Zeitschrift The journal of allergy and clinical immunology
Quellenangaben Band: 123, Heft: 6, Seiten: 1361-1370 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)
Institute of Epidemiology (EPI)
POF Topic(s) 30202 - Environmental Health

30503 - Chronic Diseases of the Lung and Allergies
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e) G-521200-001
FE 73991
G-503900-003
DOI 10.1016/j.jaci.2009.03.036
Scopus ID 67649238893
PubMed ID 19501237
Erfassungsdatum 2009-07-09
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