Meta-analysis of filaggrin polymorphisms in eczema and asthma: Robust risk factors in atopic disease - 15/08/11
, Hansjörg Baurecht, MSc b, c, , Esther Herberich c, Stefan Wagenpfeil, PhD c, Sara J. Brown, MD d, e, f, Heather J. Cordell, BA, MSc, DPhil e, Alan D. Irvine, MD f, g, Stephan Weidinger, MD a, h, ⁎ 
Reprint requests: Stephan Weidinger, MD, Department of Dermatology and Allergy, Biederstein, Technische Universität München, Biedersteiner Str. 29, 80802 Munich, Germany.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.
Le texte complet de cet article est disponible en PDF.Key words : Atopic eczema, atopic dermatitis, eczema, asthma, filaggrin, meta-analysis
Abbreviations used : FLG, OR, PAR
Plan
| Supported by grant 01GS0818 of the German Ministry of Education and Research (BMBF) as part of the National Genome Research Network (NGFN). S. Weidinger is supported by a Heisenberg fellowship (WE 2678/4-1) of the DFG, grant C49-08 of the University Hospital Rechts der Isar, Technische Universität München, and a grant from the Wilhelm-Vaillant-Stiftung. S. Weidinger and S. Wagenpfeil are supported by research grants KKF-07/04 and KKF-27/05 of the University Hospital Rechts der Isar, Technische Universität München. |
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| Disclosure of potential conflict of interest: S. Wagenpfeil has received research support from Bundesministerium für Bildung und Forschung. S. J. Brown has received research support from the British Skin Foundation, the British Society of Paediatric Dermatology, and Action Medical Research. H. J. Cordell has received research support from the Wellcome Trust, the Medical Research Council (UK), and Action Medical Research. A. D. Irvine served as a consultant for Novartis, has received research support from the Children’s Medical and Research Foundation and the Health Research Board Ireland, and has provided medicolegal consultations. The rest of the authors have declared that they have no conflict of interest. |
Vol 123 - N° 6
P. 1361 - juin 2009 Retour au numéro
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