Association between loss-of-function mutations in the filaggrin gene and self-reported food allergy and alcohol sensitivity

TY - JOUR

T1 - Association between loss-of-function mutations in the filaggrin gene and self-reported food allergy and alcohol sensitivity

AU - Linneberg, Allan René

AU - Fenger, Runa V

AU - Husemoen, Lise Lotte Nystrup

AU - Thuesen, Betina H

AU - Skaaby, Tea

AU - Gonzalez-Quintela, Arturo

AU - Vidal, Carmen

AU - Carlsen, Berit C

AU - Johansen, Jeanne D

AU - Menné, Torkil

AU - Stender, Steen

AU - Melgaard, Michael

AU - Szecsi, Pal B

AU - Berg, Nikolaj D

AU - Thyssen, Jacob P

N1 - Copyright © 2013 S. Karger AG, Basel.

PY - 2013

Y1 - 2013

N2 - Background: Loss-of-function mutations of the filaggrin (FLG) gene cause an impaired skin barrier and increase the risk of atopic dermatitis. Interestingly, FLG mutations have also been found to be associated with a high risk of peanut allergy. Objective: We investigated the association of FLG mutations with self-reported food allergy, symptoms of oral allergy syndrome (OAS), and alcohol sensitivity. Methods: A total of 3,471 adults from the general population participated in a health examination. Information on food allergies, OAS and alcohol sensitivity was obtained by questionnaire. FLG mutation carriers were defined as having at least one null mutation allele of R501X or 2282del4. Primary lactose intolerance (PLI) was defined as the C/C genotype of the rs4988235 polymorphism. Results: FLG mutations were associated with a higher risk of self-reported allergy to eggs (OR 3.22 and 95% CI 1.46-7.11), milk (OR 2.10 and 95% CI 1.12-3.92), fish (OR 4.54 and 95% CI 1.88-10.96) and wheat (OR 3.59 and 95% CI 1.61-8.02), but not with symptoms of OAS (OR 1.05 and 95% CI 0.73-1.51). Serum-specific IgE was measured in a subsample and confirmed the association between FLG and IgE to milk. A significant gene-by-gene interaction between FLG and PLI was observed in relation to self-reported allergy to milk. Furthermore, FLG mutations were associated with a higher risk of alcohol sensitivity. Conclusions: We found that loss-of-function mutations in the FLG gene were significantly associated with self-reported food allergy and alcohol sensitivity, but not with OAS. These findings, if confirmed, support the idea that skin barrier functions may be involved in the pathogenesis of food allergy.

AB - Background: Loss-of-function mutations of the filaggrin (FLG) gene cause an impaired skin barrier and increase the risk of atopic dermatitis. Interestingly, FLG mutations have also been found to be associated with a high risk of peanut allergy. Objective: We investigated the association of FLG mutations with self-reported food allergy, symptoms of oral allergy syndrome (OAS), and alcohol sensitivity. Methods: A total of 3,471 adults from the general population participated in a health examination. Information on food allergies, OAS and alcohol sensitivity was obtained by questionnaire. FLG mutation carriers were defined as having at least one null mutation allele of R501X or 2282del4. Primary lactose intolerance (PLI) was defined as the C/C genotype of the rs4988235 polymorphism. Results: FLG mutations were associated with a higher risk of self-reported allergy to eggs (OR 3.22 and 95% CI 1.46-7.11), milk (OR 2.10 and 95% CI 1.12-3.92), fish (OR 4.54 and 95% CI 1.88-10.96) and wheat (OR 3.59 and 95% CI 1.61-8.02), but not with symptoms of OAS (OR 1.05 and 95% CI 0.73-1.51). Serum-specific IgE was measured in a subsample and confirmed the association between FLG and IgE to milk. A significant gene-by-gene interaction between FLG and PLI was observed in relation to self-reported allergy to milk. Furthermore, FLG mutations were associated with a higher risk of alcohol sensitivity. Conclusions: We found that loss-of-function mutations in the FLG gene were significantly associated with self-reported food allergy and alcohol sensitivity, but not with OAS. These findings, if confirmed, support the idea that skin barrier functions may be involved in the pathogenesis of food allergy.

U2 - 10.1159/000345949

DO - 10.1159/000345949

M3 - Journal article

C2 - 23548340

SN - 1018-2438

VL - 161

SP - 234

EP - 242

JO - International Archives of Allergy and Immunology

JF - International Archives of Allergy and Immunology

IS - 3

ER -