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

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 etiolo... Full description

Journal Title: Journal of allergy and clinical immunology 2011, Vol.127 (3), p.661-667
Main Author: Brown, Sara J., MD
Other Authors: Asai, Yuka, MD , Cordell, Heather J., DPhil , Campbell, Linda E., MSc , Zhao, Yiwei, MD, PhD , Liao, Haihui, MD, PhD , Northstone, Kate, PhD , Henderson, John, MD , Alizadehfar, Reza, MD , Ben-Shoshan, Moshe, MD , Morgan, Kenneth, PhD , Roberts, Graham, DM , Masthoff, Laury J.N., MD , Pasmans, Suzanne G.M.A., MD, PhD , van den Akker, Peter C., MD , Wijmenga, Cisca, PhD , Hourihane, Jonathan O’B., PhD , Palmer, Colin N.A., PhD , Lack, Gideon, PhD , Clarke, Ann, MD, MSc , Hull, Peter R., MD, PhD , Irvine, Alan D., MD , McLean, W. H. Irwin, PhD, DSc
Format: Electronic Article Electronic Article
Language: English
Subjects:
IgE
Quelle: Alma/SFX Local Collection
Publisher: United States: Elsevier Inc
ID: ISSN: 0091-6749
Link: https://www.ncbi.nlm.nih.gov/pubmed/21377035
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title: Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy
format: Article
creator:
  • Brown, Sara J., MD
  • Asai, Yuka, MD
  • Cordell, Heather J., DPhil
  • Campbell, Linda E., MSc
  • Zhao, Yiwei, MD, PhD
  • Liao, Haihui, MD, PhD
  • Northstone, Kate, PhD
  • Henderson, John, MD
  • Alizadehfar, Reza, MD
  • Ben-Shoshan, Moshe, MD
  • Morgan, Kenneth, PhD
  • Roberts, Graham, DM
  • Masthoff, Laury J.N., MD
  • Pasmans, Suzanne G.M.A., MD, PhD
  • van den Akker, Peter C., MD
  • Wijmenga, Cisca, PhD
  • Hourihane, Jonathan O’B., PhD
  • Palmer, Colin N.A., PhD
  • Lack, Gideon, PhD
  • Clarke, Ann, MD, MSc
  • Hull, Peter R., MD, PhD
  • Irvine, Alan D., MD
  • McLean, W. H. Irwin, PhD, DSc
subjects:
  • AD, Atopic dermatitis
  • Allergens
  • Allergies
  • Allergy
  • Allergy and Immunology
  • ALSPAC, Avon Longitudinal Study of Parents and Children
  • Arachis hypogaea
  • ASTHMA
  • ATOPIC-DERMATITIS
  • Avon Longitudinal Study of Parents
  • beverages
  • Canada
  • Case-Control Studies
  • CHILDHOOD
  • CHILDREN
  • Children & youth
  • Dermatitis
  • ECZEMA
  • Etiology
  • Europe
  • Filaggrin
  • Filaggrin Proteins
  • FLG, Filaggrin
  • food
  • Food allergies
  • Food allergy
  • FOOD CHALLENGES
  • Food hypersensitivity
  • Genetic Association Studies
  • Genetic engineering
  • Genetic Predisposition to Disease
  • Genetic research
  • Genetic Variation
  • Health aspects
  • Heritability
  • Humans
  • Hypersensitivity
  • Hypersensitivity, Immediate
  • IgE
  • Immunoglobulin E
  • Immunology
  • Intermediate Filament Proteins - genetics
  • Ireland
  • MANAGEMENT
  • Medical colleges
  • Mutation
  • Netherlands
  • Nuts
  • Odds ratio
  • OR, Odds ratio
  • Peanut allergy
  • Peanut Hypersensitivity - genetics
  • Peanuts
  • PREVALENCE
  • PRICK
  • Replication
  • Respiratory agents
  • risk factor
  • Risk Factors
  • SKIN BARRIER FUNCTION
  • Skin prick test
  • Skin tests
  • Special section
  • SPT, Skin prick test
  • UK, United Kingdom
  • UMCG Approved
  • United Kingdom
ispartof: Journal of allergy and clinical immunology, 2011, Vol.127 (3), p.661-667
description: 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.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0091-6749
fulltext: fulltext
issn:
  • 0091-6749
  • 1097-6825
url: Link


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titleLoss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy
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creatorBrown, Sara J., MD ; Asai, Yuka, MD ; Cordell, Heather J., DPhil ; Campbell, Linda E., MSc ; Zhao, Yiwei, MD, PhD ; Liao, Haihui, MD, PhD ; Northstone, Kate, PhD ; Henderson, John, MD ; Alizadehfar, Reza, MD ; Ben-Shoshan, Moshe, MD ; Morgan, Kenneth, PhD ; Roberts, Graham, DM ; Masthoff, Laury J.N., MD ; Pasmans, Suzanne G.M.A., MD, PhD ; van den Akker, Peter C., MD ; Wijmenga, Cisca, PhD ; Hourihane, Jonathan O’B., PhD ; Palmer, Colin N.A., PhD ; Lack, Gideon, PhD ; Clarke, Ann, MD, MSc ; Hull, Peter R., MD, PhD ; Irvine, Alan D., MD ; McLean, W. H. Irwin, PhD, DSc
creatorcontribBrown, Sara J., MD ; Asai, Yuka, MD ; Cordell, Heather J., DPhil ; Campbell, Linda E., MSc ; Zhao, Yiwei, MD, PhD ; Liao, Haihui, MD, PhD ; Northstone, Kate, PhD ; Henderson, John, MD ; Alizadehfar, Reza, MD ; Ben-Shoshan, Moshe, MD ; Morgan, Kenneth, PhD ; Roberts, Graham, DM ; Masthoff, Laury J.N., MD ; Pasmans, Suzanne G.M.A., MD, PhD ; van den Akker, Peter C., MD ; Wijmenga, Cisca, PhD ; Hourihane, Jonathan O’B., PhD ; Palmer, Colin N.A., PhD ; Lack, Gideon, PhD ; Clarke, Ann, MD, MSc ; Hull, Peter R., MD, PhD ; Irvine, Alan D., MD ; McLean, W. H. Irwin, PhD, DSc
descriptionBackground 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.
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1EISSN: 1097-6825
2DOI: 10.1016/j.jaci.2011.01.031
3PMID: 21377035
languageeng
publisherUnited States: Elsevier Inc
subjectAD, Atopic dermatitis ; Allergens ; Allergies ; Allergy ; Allergy and Immunology ; ALSPAC, Avon Longitudinal Study of Parents and Children ; Arachis hypogaea ; ASTHMA ; ATOPIC-DERMATITIS ; Avon Longitudinal Study of Parents ; beverages ; Canada ; Case-Control Studies ; CHILDHOOD ; CHILDREN ; Children & youth ; Dermatitis ; ECZEMA ; Etiology ; Europe ; Filaggrin ; Filaggrin Proteins ; FLG, Filaggrin ; food ; Food allergies ; Food allergy ; FOOD CHALLENGES ; Food hypersensitivity ; Genetic Association Studies ; Genetic engineering ; Genetic Predisposition to Disease ; Genetic research ; Genetic Variation ; Health aspects ; Heritability ; Humans ; Hypersensitivity ; Hypersensitivity, Immediate ; IgE ; Immunoglobulin E ; Immunology ; Intermediate Filament Proteins - genetics ; Ireland ; MANAGEMENT ; Medical colleges ; Mutation ; Netherlands ; Nuts ; Odds ratio ; OR, Odds ratio ; Peanut allergy ; Peanut Hypersensitivity - genetics ; Peanuts ; PREVALENCE ; PRICK ; Replication ; Respiratory agents ; risk factor ; Risk Factors ; SKIN BARRIER FUNCTION ; Skin prick test ; Skin tests ; Special section ; SPT, Skin prick test ; UK, United Kingdom ; UMCG Approved ; United Kingdom
ispartofJournal of allergy and clinical immunology, 2011, Vol.127 (3), p.661-667
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0American Academy of Allergy, Asthma & Immunology
12011 American Academy of Allergy, Asthma & Immunology
2info:eu-repo/semantics/restrictedAccess
3Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
4COPYRIGHT 2011 Elsevier B.V.
5Copyright Elsevier Limited Mar 2011
62011 Mosby, Inc. 2011 American Academy of Allergy, Asthma & Immunology
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0Brown, Sara J., MD
1Asai, Yuka, MD
2Cordell, Heather J., DPhil
3Campbell, Linda E., MSc
4Zhao, Yiwei, MD, PhD
5Liao, Haihui, MD, PhD
6Northstone, Kate, PhD
7Henderson, John, MD
8Alizadehfar, Reza, MD
9Ben-Shoshan, Moshe, MD
10Morgan, Kenneth, PhD
11Roberts, Graham, DM
12Masthoff, Laury J.N., MD
13Pasmans, Suzanne G.M.A., MD, PhD
14van den Akker, Peter C., MD
15Wijmenga, Cisca, PhD
16Hourihane, Jonathan O’B., PhD
17Palmer, Colin N.A., PhD
18Lack, Gideon, PhD
19Clarke, Ann, MD, MSc
20Hull, Peter R., MD, PhD
21Irvine, Alan D., MD
22McLean, W. H. Irwin, PhD, DSc
title
0Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy
1Journal of allergy and clinical immunology
addtitleJ Allergy Clin Immunol
descriptionBackground 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.
subject
0AD, Atopic dermatitis
1Allergens
2Allergies
3Allergy
4Allergy and Immunology
5ALSPAC, Avon Longitudinal Study of Parents and Children
6Arachis hypogaea
7ASTHMA
8ATOPIC-DERMATITIS
9Avon Longitudinal Study of Parents
10beverages
11Canada
12Case-Control Studies
13CHILDHOOD
14CHILDREN
15Children & youth
16Dermatitis
17ECZEMA
18Etiology
19Europe
20Filaggrin
21Filaggrin Proteins
22FLG, Filaggrin
23food
24Food allergies
25Food allergy
26FOOD CHALLENGES
27Food hypersensitivity
28Genetic Association Studies
29Genetic engineering
30Genetic Predisposition to Disease
31Genetic research
32Genetic Variation
33Health aspects
34Heritability
35Humans
36Hypersensitivity
37Hypersensitivity, Immediate
38IgE
39Immunoglobulin E
40Immunology
41Intermediate Filament Proteins - genetics
42Ireland
43MANAGEMENT
44Medical colleges
45Mutation
46Netherlands
47Nuts
48Odds ratio
49OR, Odds ratio
50Peanut allergy
51Peanut Hypersensitivity - genetics
52Peanuts
53PREVALENCE
54PRICK
55Replication
56Respiratory agents
57risk factor
58Risk Factors
59SKIN BARRIER FUNCTION
60Skin prick test
61Skin tests
62Special section
63SPT, Skin prick test
64UK, United Kingdom
65UMCG Approved
66United Kingdom
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5Liao, Haihui, MD, PhD
6Northstone, Kate, PhD
7Henderson, John, MD
8Alizadehfar, Reza, MD
9Ben-Shoshan, Moshe, MD
10Morgan, Kenneth, PhD
11Roberts, Graham, DM
12Masthoff, Laury J.N., MD
13Pasmans, Suzanne G.M.A., MD, PhD
14van den Akker, Peter C., MD
15Wijmenga, Cisca, PhD
16Hourihane, Jonathan O’B., PhD
17Palmer, Colin N.A., PhD
18Lack, Gideon, PhD
19Clarke, Ann, MD, MSc
20Hull, Peter R., MD, PhD
21Irvine, Alan D., MD
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titleLoss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy
authorBrown, Sara J., MD ; Asai, Yuka, MD ; Cordell, Heather J., DPhil ; Campbell, Linda E., MSc ; Zhao, Yiwei, MD, PhD ; Liao, Haihui, MD, PhD ; Northstone, Kate, PhD ; Henderson, John, MD ; Alizadehfar, Reza, MD ; Ben-Shoshan, Moshe, MD ; Morgan, Kenneth, PhD ; Roberts, Graham, DM ; Masthoff, Laury J.N., MD ; Pasmans, Suzanne G.M.A., MD, PhD ; van den Akker, Peter C., MD ; Wijmenga, Cisca, PhD ; Hourihane, Jonathan O’B., PhD ; Palmer, Colin N.A., PhD ; Lack, Gideon, PhD ; Clarke, Ann, MD, MSc ; Hull, Peter R., MD, PhD ; Irvine, Alan D., MD ; McLean, W. H. Irwin, PhD, DSc
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0AD, Atopic dermatitis
1Allergens
2Allergies
3Allergy
4Allergy and Immunology
5ALSPAC, Avon Longitudinal Study of Parents and Children
6Arachis hypogaea
7ASTHMA
8ATOPIC-DERMATITIS
9Avon Longitudinal Study of Parents
10beverages
11Canada
12Case-Control Studies
13CHILDHOOD
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15Children & youth
16Dermatitis
17ECZEMA
18Etiology
19Europe
20Filaggrin
21Filaggrin Proteins
22FLG, Filaggrin
23food
24Food allergies
25Food allergy
26FOOD CHALLENGES
27Food hypersensitivity
28Genetic Association Studies
29Genetic engineering
30Genetic Predisposition to Disease
31Genetic research
32Genetic Variation
33Health aspects
34Heritability
35Humans
36Hypersensitivity
37Hypersensitivity, Immediate
38IgE
39Immunoglobulin E
40Immunology
41Intermediate Filament Proteins - genetics
42Ireland
43MANAGEMENT
44Medical colleges
45Mutation
46Netherlands
47Nuts
48Odds ratio
49OR, Odds ratio
50Peanut allergy
51Peanut Hypersensitivity - genetics
52Peanuts
53PREVALENCE
54PRICK
55Replication
56Respiratory agents
57risk factor
58Risk Factors
59SKIN BARRIER FUNCTION
60Skin prick test
61Skin tests
62Special section
63SPT, Skin prick test
64UK, United Kingdom
65UMCG Approved
66United Kingdom
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5Liao, Haihui, MD, PhD
6Northstone, Kate, PhD
7Henderson, John, MD
8Alizadehfar, Reza, MD
9Ben-Shoshan, Moshe, MD
10Morgan, Kenneth, PhD
11Roberts, Graham, DM
12Masthoff, Laury J.N., MD
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15Wijmenga, Cisca, PhD
16Hourihane, Jonathan O’B., PhD
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20Hull, Peter R., MD, PhD
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ristypeJOUR
atitleLoss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy
jtitleJournal of allergy and clinical immunology
addtitleJ Allergy Clin Immunol
date2011
risdate2011
volume127
issue3
spage661
epage667
pages661-667
issn0091-6749
eissn1097-6825
notesThese authors contributed equally to this work.
abstractBackground 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.
copUnited States
pubElsevier Inc
pmid21377035
doi10.1016/j.jaci.2011.01.031
oafree_for_read