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.
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.
Authors: Adrian Chan; William Terry; Hongmei Zhang; Wilfried Karmaus; Susan Ewart; John W Holloway; Graham Roberts; Ramesh Kurukulaaratchy; Syed Hasan Arshad Journal: Clin Exp Allergy Date: 2018-02 Impact factor: 5.018
Authors: Neil E Rice; Bipen D Patel; Iain A Lang; Meena Kumari; Timothy M Frayling; Anna Murray; David Melzer Journal: J Allergy Clin Immunol Date: 2008-08-29 Impact factor: 10.793