Filaggrin mutations confer susceptibility to atopic dermatitis but not to asthma.
BACKGROUND
Loss-of-function mutations in the filaggrin gene (FLG) have been strongly associated with atopic dermatitis and allergic phenotypes in multiple populations. The role of these mutations in the development of asthma is less clear, particularly in patients who do not have coincident atopic dermatitis.


OBJECTIVE
To determine whether FLG mutations are associated with asthma or asthma-related intermediate phenotypes.


METHODS
We genotyped 2 loss-of-function FLG mutations (R501X and 2282del4) in white children (age 5-12 years) with mild to moderate asthma in the Childhood Asthma Management Program. We assessed the relationship of these mutations to asthma and allergy-related phenotypes in children with and without atopic dermatitis using both population-based and family-based tests of association.


RESULTS
Nearly 1/3 (185/646) of the participating children had atopic dermatitis. Although strong associations were observed between FLG mutations and atopic dermatitis (odds ratio, 2.4; P = 7.6 x 10(-5)) and between the mutations and total serum IgE level (P = .009 in the atopic dermatitis cohort), no association was noted with either asthma or asthma-related phenotypes, including FEV(1), FEV(1)/forced vital capacity, and methacholine PC(20) (P > .1 for all tests).


CONCLUSIONS
Although FLG loss-of-function mutations are consistently associated with atopic dermatitis and other allergic phenotypes, these mutations do not appear to influence either susceptibility to asthma or asthma severity phenotypes.


CONCLUSIONS
Filaggrin mutations that predispose to atopic dermatitis do not modulate the asthma phenotype.
Rogers
Angela J
AJ
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Celedón
Juan C
JC
Lasky-Su
Jessica A
JA
Weiss
Scott T
ST
Raby
Benjamin A
BA
D001249:Asthma / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000378:metabolism; D005260:Female; D000091344:Filaggrin Proteins; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000502:physiology; D008297:Male; D010641:Phenotype; D017384:Sequence Deletion; D012720:Severity of Illness Index
D018389:Codon, Nonsense; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins