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

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 × 10(-6); odds ratio, 5.3; 95% CI, 2.8-10.2), and this association was replicated in the Canadian study (P = 5.4 × 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.

• Authors: Sara J Brown, 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
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 127 Issue 3 Pg. 661-7 (Mar 2011) ISSN: 1097-6825 [Electronic] United States
• PMID: 21377035 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Chemical References

• FLG protein, human
• Filaggrin Proteins
• Intermediate Filament Proteins

Topics

• Canada
• Case-Control Studies
• Europe
• Filaggrin Proteins
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genetic Variation
• Humans
• Hypersensitivity, Immediate
• Intermediate Filament Proteins (genetics)
• Ireland
• Netherlands
• Peanut Hypersensitivity (genetics)
• Risk Factors