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

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

Research output: Contribution to journalArticle

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Authors

  • 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 Clarke
  • Peter R. Hull
  • Alan D. Irvine
  • W. H. Irwin McLean

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Info

Original languageEnglish
Pages661-667
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Journal publication dateMar 2011
Journal number3
Volume127
DOIs
StatePublished

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.)

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