Filaggrin null mutations are associated with increased asthma severity in children and young adults.

Background: Filaggrin is a key protein involved in skin barrier function. Filaggrin (FLG) null mutations are important genetic predisposing factors for atopic disease.

Objective: To study the role of FLG null alleles in the clinical phenotype in children and young adults with asthma.

Methods: FLG mutations R501X and 2282del4 were assayed in 874 subjects 3 to 22 years old with asthma from Tayside. Lung function and disease severity were also studied.

Results: The filaggrin mutations were significantly associated with greater disease severity for asthma. Independent of eczema, mean FEV(1)/forced vital capacity of FLG wild-type individuals differed from those carrying either FLG null allele (0.89 vs 0.86; P = .012). Individuals bearing FLG null alleles were more likely to be prescribed increased medication (chi(2) = 10.3; P = .001), with the homozygote null individuals having an odds ratio of 6.68 (95% CI, 1.7-27.0; P = .008) for being prescribed long-acting beta-agonists in addition to inhaled steroids. FLG null alleles were also associated with increased rescue medication use (P = .004). Individuals with asthma and with FLG null alleles were more likely to have eczema, and individuals with eczema tended to have more severe asthma; however, the association of FLG null alleles with all markers of asthma disease severity was similar in children with and without eczema.

Conclusion: FLG mutations are associated not only with eczema-associated asthma susceptibility but also with asthma severity independent of eczema status.

Clinical Implications: FLG status influences controller and reliever medication requirements in children and young adults with asthma.