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


OBJECTIVE
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.
Rodríguez
Elke
E
Division of Environmental Dermatology and Allergy, Helmholtz Zentrum Munich and ZAUM-Center for Allergy and Environment, Technische Universität München, Munich, Germany.
Baurecht
Hansjörg
H
Herberich
Esther
E
Wagenpfeil
Stefan
S
Brown
Sara J
SJ
Cordell
Heather J
HJ
Irvine
Alan D
AD
Weidinger
Stephan
S
D000483:Alleles; D001249:Asthma / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004485:Eczema / Q000453:epidemiology / Q000235:genetics*; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins