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

TY - JOUR

T1 - Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy

AU - Brown, Sara J.

AU - Asai, Yuka

AU - Cordell, Heather J.

AU - Campbell, Linda E.

AU - Zhao, Yiwei

AU - Liao, Haihui

AU - Northstone, Kate

AU - Henderson, John

AU - Alizadehfar, Reza

AU - Ben-Shoshan, Moshe

AU - Morgan, Kenneth

AU - Roberts, Graham

AU - Masthoff, Laury J. N.

AU - Pasmans, Suzanne G. M. A.

AU - van den Akker, Peter C.

AU - Wijmenga, Cisca

AU - Hourihane, Jonathan O'B.

AU - Palmer, Colin N. A.

AU - Lack, Gideon

AU - Clarke, Ann

AU - Hull, Peter R.

AU - Irvine, Alan D.

AU - McLean, W. H. Irwin

PY - 2011/3

Y1 - 2011/3

N2 - 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.)

AB - 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.)

KW - Atopic dermatitis

KW - filaggrin

KW - IgE

KW - peanut allergy

KW - risk factor

KW - SKIN BARRIER FUNCTION

KW - ATOPIC-DERMATITIS

KW - FOOD CHALLENGES

KW - CHILDREN

KW - ECZEMA

KW - PRICK

KW - PREVALENCE

KW - ASTHMA

KW - MANAGEMENT

KW - CHILDHOOD

UR - https://www.scopus.com/pages/publications/79952286850

U2 - 10.1016/j.jaci.2011.01.031

DO - 10.1016/j.jaci.2011.01.031

M3 - Article

C2 - 21377035

SN - 0091-6749

VL - 127

SP - 661

EP - 667

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 3

ER -