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

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Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. / Brown, Sara J. (Lead / Corresponding author); 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 journalArticle

Harvard

Brown, SJ, Asai, Y, Cordell, HJ, Campbell, LE, Zhao, Y, Liao, H, Northstone, K, Henderson, J, Alizadehfar, R, Ben-Shoshan, M, Morgan, K, Roberts, G, Masthoff, LJN, Pasmans, SGMA, van den Akker, PC, Wijmenga, C, Hourihane, JOB, Palmer, CNA, Lack, G, Clarke, A, Hull, PR, Irvine, AD & McLean, WHI 2011, 'Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy' Journal of Allergy and Clinical Immunology, vol 127, no. 3, pp. 661-667.

APA

Brown, S. J., Asai, Y., Cordell, H. J., Campbell, L. E., Zhao, Y., Liao, H., Northstone, K., Henderson, J., Alizadehfar, R., Ben-Shoshan, M., Morgan, K., Roberts, G., Masthoff, L. J. N., Pasmans, S. G. M. A., van den Akker, P. C., Wijmenga, C., Hourihane, J. O. B., Palmer, C. N. A., Lack, G., Clarke, A., Hull, P. R., Irvine, A. D., & McLean, W. H. I. (2011). Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. Journal of Allergy and Clinical Immunology, 127(3), 661-667doi: 10.1016/j.jaci.2011.01.031

Vancouver

Brown SJ, Asai Y, Cordell HJ, Campbell LE, Zhao Y, Liao H et al. Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. Journal of Allergy and Clinical Immunology. 2011 Mar;127(3):661-667.

Author

Brown, Sara J. (Lead / Corresponding author); 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 / Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.

In: Journal of Allergy and Clinical Immunology, Vol. 127, No. 3, 03.2011, p. 661-667.

Research output: Contribution to journalArticle

Bibtex - Download

@article{bf4efdf708d940d7bfa9da5a84819159,
title = "Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy",
author = "Brown, {Sara J.} and Yuka Asai and Cordell, {Heather J.} and Campbell, {Linda E.} and Yiwei Zhao and Haihui Liao and Kate Northstone and John Henderson and Reza Alizadehfar and Moshe Ben-Shoshan and Kenneth Morgan and Graham Roberts and Masthoff, {Laury J. N.} and Pasmans, {Suzanne G. M. A.} and {van den Akker}, {Peter C.} and Cisca Wijmenga and Hourihane, {Jonathan O'B.} and Palmer, {Colin N. A.} and Gideon Lack and Ann Clarke and Hull, {Peter R.} and Irvine, {Alan D.} and McLean, {W. H. Irwin}",
year = "2011",
volume = "127",
number = "3",
pages = "661--667",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",

}

RIS (suitable for import to EndNote) - Download

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 &gt;= 8 mm and/or peanut-specific IgE &gt;= 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 &gt;= 8 mm and/or peanut-specific IgE &gt;= 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 -

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