Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy

Sara J. Brown (Lead / Corresponding author), Yuka Asai, Heather J. Cordell, Linda E. Campbell, Yiwei Zhao, Haihui Liao, Kate Northstone, John Henderson, Reza Alizadehfar, Moshe Ben-Shoshan, Kenneth Morgan, Graham Roberts, Laury J. N. Masthoff, Suzanne G. M. A. Pasmans, Peter C. van den Akker, Cisca Wijmenga, Jonathan O'B. Hourihane, Colin N. A. Palmer, Gideon Lack, Ann ClarkePeter R. Hull, Alan D. Irvine, W. H. Irwin McLean

    Research output: Contribution to journalArticlepeer-review

    290 Citations (Scopus)
    135 Downloads (Pure)

    Abstract

    Background: IgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the etiology of peanut allergy.

    Objective: To investigate the association between filaggrin loss-of-function mutations and peanut allergy.

    Methods: Case-control study of 71 English, Dutch, and Irish oral food challenge-positive patients with peanut allergy and 1000 non peanut-sensitized English population controls. Replication was tested in 390 white Canadian patients with peanut allergy (defined by food challenge, or clinical history and skin prick test wheal to peanut >= 8 mm and/or peanut-specific IgE >= 15 kUL(-1)) and 891 white Canadian population controls. The most prevalent filaggrin loss-of-function mutations were assayed in each population: R501X and 2282del4 in the Europeans, and R501X, 2282del4, R2447X, and S3247X in the Canadians. The Fisher exact test and logistic regression were used to test for association; covariate analysis controlled for coexistent atopic dermatitis.

    Results: Filaggrin loss-of-function mutations showed a strong and significant association with peanut allergy in the food challenge-positive patients (P = 3.0 x 10(-6); odds ratio, 5.3; 95% CI, 2.8-10.2), and this association was replicated in the Canadian study (P = 5.4 x 10(-5); odds ratio, 1.9; 95% CI, 1.4-2.6). The association of filaggrin mutations with peanut allergy remains significant (P = .0008) after controlling for coexistent atopic dermatitis.

    Conclusion: Filaggrin mutations represent a significant risk factor for IgE-mediated peanut allergy, indicating a role for epithelial barrier dysfunction in the pathogenesis of this disease. (J Allergy Clin Immunol 2011;127:661-7.)

    Original languageEnglish
    Pages (from-to)661-667
    Number of pages7
    JournalJournal of Allergy and Clinical Immunology
    Volume127
    Issue number3
    DOIs
    Publication statusPublished - Mar 2011

    Keywords

    • Atopic dermatitis
    • filaggrin
    • IgE
    • peanut allergy
    • risk factor
    • SKIN BARRIER FUNCTION
    • ATOPIC-DERMATITIS
    • FOOD CHALLENGES
    • CHILDREN
    • ECZEMA
    • PRICK
    • PREVALENCE
    • ASTHMA
    • MANAGEMENT
    • CHILDHOOD

    Fingerprint

    Dive into the research topics of 'Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy'. Together they form a unique fingerprint.

    Cite this