Filaggrin mutations in the onset of eczema, sensitization, asthma, hay fever and the interaction with cat exposure.
BACKGROUND
Filaggrin gene (FLG) mutations contribute to the development of eczema and asthma, but their contribution to sensitization and hay fever remains unclear.


METHODS
FLG mutations R501X, 2282del4 and R2447X were genotyped in the Prevention and Incidence of Asthma and Mite Allergy birth cohort (n = 934) to evaluate longitudinally, for up to 8 years, their association with eczema, sensitization, asthma, hay fever and their interaction with cat exposure.


RESULTS
The combined FLG mutations were significantly associated with eczema at all ages when occurring in the first year of life (OR = 2.0; 95% CI: 1.4-2.8). Combined FLG mutations were associated with both atopic and nonatopic eczema, as well as asthma (OR = 3.7; 95% CI: 1.8-7.5). When the FLG 2282del4 mutation was analysed separately, it was significantly associated with the development of eczema during the first year, having eczema up to 8 years and sensitization at the age of 8 years, which was enhanced by early-life cat exposure (ORs being 8.2; 95% CI: 2.6-25.9, 6.0; 95% CI: 3.2-11.3 and 5.4; 95% CI: 1.2-23.6 respectively). FLG 2282del4 was significantly associated with hay fever from the age 5 years onwards (OR = 3.9; 95% CI: 1.5-10.5).


CONCLUSIONS
FLG mutations are associated both with atopic and nonatopic eczema starting in the first year of life. FLG mutations combined with eczema in the first year of life are associated with a later development of asthma and hay fever, a clear example of the atopic march. We confirm that cat exposure enhances the effect of a FLG mutation on the development of eczema and sensitization.
Departments of Dermatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
M L A
ML
Schuttelaar
M
M
Kerkhof
M F
MF
Jonkman
G H
GH
Koppelman
B
B
Brunekreef
J C
JC
de Jongste
A
A
Wijga
W H I
WH
McLean
D S
DS
Postma
D000818:Animals; D001249:Asthma / Q000235:genetics*; D002415:Cats; D002648:Child; D002675:Child, Preschool; D004485:Eczema / Q000235:genetics*; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D019570:Inhalation Exposure / Q000009:adverse effects*; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008137:Longitudinal Studies; D009154:Mutation; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics*
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins