Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. / Brown, Sara J.; Asai, Yuka; Cordell, Heather J.; Campbell, Linda E.; Zhao, Yiwei; Liao, Haihui; Northstone, Kate; Henderson, John; Alizadehfar, Reza; Ben-Shoshan, Moshe; Morgan, Kenneth; Roberts, Graham; Masthoff, Laury J. N.; Pasmans, Suzanne G. M. A.; van den Akker, Peter C.; Wijmenga, Cisca; Hourihane, Jonathan O'B.; Palmer, Colin N. A.; Lack, Gideon; Clarke, Ann; Hull, Peter R.; Irvine, Alan D.; McLean, W. H. Irwin.
In: Journal of Allergy and Clinical Immunology, Vol. 127, No. 3, 03.2011, p. 661-667.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy
A1 - Brown,Sara J.
A1 - Asai,Yuka
A1 - Cordell,Heather J.
A1 - Campbell,Linda E.
A1 - Zhao,Yiwei
A1 - Liao,Haihui
A1 - Northstone,Kate
A1 - Henderson,John
A1 - Alizadehfar,Reza
A1 - Ben-Shoshan,Moshe
A1 - Morgan,Kenneth
A1 - Roberts,Graham
A1 - Masthoff,Laury J. N.
A1 - Pasmans,Suzanne G. M. A.
A1 - van den Akker,Peter C.
A1 - Wijmenga,Cisca
A1 - Hourihane,Jonathan O'B.
A1 - Palmer,Colin N. A.
A1 - Lack,Gideon
A1 - Clarke,Ann
A1 - Hull,Peter R.
A1 - Irvine,Alan D.
A1 - McLean,W. H. Irwin
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 - <p>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.</p><p>Objective: To investigate the association between filaggrin loss-of-function mutations and peanut allergy.</p><p>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.</p><p>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.</p><p>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.)</p>
AB - <p>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.</p><p>Objective: To investigate the association between filaggrin loss-of-function mutations and peanut allergy.</p><p>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.</p><p>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.</p><p>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.)</p>
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
U2 - 10.1016/j.jaci.2011.01.031
DO - 10.1016/j.jaci.2011.01.031
M1 - Article
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 3
VL - 127
SP - 661
EP - 667
ER -