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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:120

Article

Palmer, Colin N. A. ; Ismail, Tahmina ; Lee, Simon P. ; Terron-Kwiatkowski, Ana ; Zhao, Yiwei ; Liao, Haihui ; Smith, Frances J. D. ; McLean, W. H. Irwin ; Mukhopadhyay, Somnath

关键词: skin barrier;    asthma;    atopy;    eczema;    keratinization;    treatment;    control;    lung function;   

DOI  :  10.1016/j.jaci.2007.04.001

来源: Elsevier

【 摘 要 】

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 FEV1/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 P-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.

【 授权许可】

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