Filaggrin loss-of-function variants are associated with atopic comorbidity in pediatric inflammatory bowel disease.
BACKGROUND
Pediatric inflammatory bowel disease (IBD) has a high prevalence of coexistent atopy. Filaggrin (FLG) loss-of-function variants (null-alleles) are associated with eczema and asthma in association with eczema. The aim was to assess the contribution of FLG null-alleles to pediatric IBD susceptibility and to coexistent atopy (eczema, asthma, allergic rhinitis, or food allergy).


METHODS
FLG variants (R501X and 2282del4) were genotyped in 403 children with IBD, 683 parents, and 996 population controls.


RESULTS
In all, 11% of IBD patients carried at least 1 FLG null-allele compared to 11% of population controls (P > 0.4). Carriage of 1 or more null-alleles in patients with atopy (present in 52% of IBD patients) differed from IBD patients without atopy (14% versus 6%, P = 0.01; odds ratio [OR] 2.4, 95% confidence interval [CI] 1.2-5.1). The effect of FLG null-alleles was strongest for eczema (19% versus 7%, P = 0.0003; OR 3.3, 95% CI 1.7-6.6) and food allergy (28% versus 8%, P = 0.0001; OR 4.5, 95% CI 2.0-10.0). The presence of more than 1 atopic disease tended to increase the associated OR: eczema + asthma (23% versus 7%, P = 0.001; OR 3.9, 95% CI 1.6-9.1), eczema + asthma + allergic rhinitis (29% versus 7%, P = 0.0006; OR 5.4, 95% CI 1.9-15.4) and eczema + asthma + allergic rhinitis + food allergy (45% versus 6%, P < 10(-4); OR 12.2, 95% CI 3.2-46.3). Logistic regression analysis of IBD cases confirmed the association of carriage of an FLG null-allele with atopy (P = 0.01; OR 2.4, 95% CI 1.2-5.1) and co-occurrence of different forms of atopy (P = 0.003; OR 3.5, 95% CI 1.5-8.1).


CONCLUSIONS
Filaggrin null-alleles have no effect on IBD susceptibility but contribute to coexistent eczema and food allergy.
Van Limbergen
J
J
Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. johanvanlimbergen@hotmail.com
Russell
R K
RK
Nimmo
E R
ER
Zhao
Y
Y
Liao
H
H
Drummond
H E
HE
Davies
G
G
Gillett
P M
PM
McGrogan
P
P
Bisset
W M
WM
Mahdi
G
G
Wilson
D C
DC
Brown
S J
SJ
McLean
W H I
WH
Satsangi
J
J
D000293:Adolescent; D001249:Asthma / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D015897:Comorbidity; D004485:Eczema / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D000091344:Filaggrin Proteins; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000235:genetics*; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins