An interaction between filaggrin mutations and early food sensitization improves the prediction of childhood asthma.
BACKGROUND
Asthma prediction in early infancy is essential for the development of new preventive strategies. Loss-of-function mutations in the filaggrin gene (FLG) were identified as risk factors for eczema and associated asthma.


OBJECTIVE
We evaluated the utility of the FLG mutations for the prediction of asthma.


METHODS
Eight hundred seventy-one individuals of the prospective German Multicenter Allergy Study cohort were genotyped for 3 FLG mutations. Information on asthma, eczema, and food sensitization was available from birth to 13 years of age. Pulmonary function was measured from 7 to 13 years of age. The predictive value of the FLG mutations and of atopic phenotypes in infancy was assessed for asthma.


RESULTS
In infants with eczema and sensitization to food allergens, the FLG mutations predicted childhood asthma with a positive predictive value of 100% (95% CI, 65.5% to 100%). This subgroup was characterized by a significant decrease in pulmonary function until puberty and represented 8.1% of all asthmatic children and 19.1% of patients with asthma after infantile eczema. We found a strong synergistic interaction between the FLG-null alleles and early food sensitization in the disease transition from eczema to asthma (relative excess risk due to interaction, 2.64; 95% CI, 1.70-3.98; P = .00040).


CONCLUSIONS
FLG mutations and food sensitization represent 2 distinct mechanisms interacting in the pathogenesis of asthma. In infants with eczema and food sensitization, genotyping of the FLG mutations allows the prediction of asthma before the onset of symptoms. Our findings might facilitate the development of early subgroup-specific interventions to prevent the progression from eczema to asthma.
Marenholz
Ingo
I
Max-Delbrück-Centrum (MDC) for Molecular Medicine, Berlin, Germany.
Kerscher
Tamara
T
Bauerfeind
Anja
A
Esparza-Gordillo
Jorge
J
Nickel
Renate
R
Keil
Thomas
T
Lau
Susanne
S
Rohde
Klaus
K
Wahn
Ulrich
U
Lee
Young-Ae
YA
D000293:Adolescent; D001249:Asthma / Q000209:etiology* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004485:Eczema / Q000150:complications; D005260:Female; D000091344:Filaggrin Proteins; D005512:Food Hypersensitivity / Q000150:complications*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007223:Infant; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008168:Lung / Q000503:physiopathology; D008297:Male; D009154:Mutation; D012307:Risk Factors
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D007073:Immunoglobulin E