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Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence

Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence
Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence
Background

Filaggrin is an epidermal protein that has a role in skin barrier function. Filaggrin loss-of-function (FLG-LOF) mutations are a significant risk factor for eczema and atopy, but their association with food allergy (FA) is less clear.

Objective

We explored the longitudinal relationship between 3 common FLG-LOF mutations and FA using the Isle of Wight birth cohort.

Methods

FA diagnosis was based on recognized allergic reactions within 4 hours after exposure to known food allergens. Food allergen sensitization (FAS) was identified by using skin prick tests conducted between 1 and 18 years of age to a range of food allergens. Three FLG mutations were genotyped in 1150 (79%) of 1456 children. The temporal relationships between FA, FAS, and eczema in children with FLG mutations were explored by using path analysis with total, direct, and indirect effect models.

Results

There was a significant total effect of FLG-LOF mutations on the risk of FA in later childhood at the ages of 10 (odds ratio, 31.46; 95% CI, 2.86 to >100) and 18 (odds ratio, 4.25; 95% CI, 1.55-11.61) years. Path analysis showed that there was no direct effect of FLG-LOF mutations on FA at any age; however, an indirect effect was found on FA at all ages through eczema and FAS in the earlier years.

Conclusion

FLG-LOF mutations are associated with FA in older children through eczema and FAS during early childhood. Our results highlight a biologically plausible pathway, which suggests that skin barrier function is important in the development and persistence of FA.
food allergy, filaggrin, FLG-LOF, food allergen sensitization, path analysis, prediction, eczema
0091-6749
876-882.e4
Venkataraman, Devasmitha
5d80518f-95d4-4872-8af7-095d77e1121b
Soto-Ramírez, Nelís
3526295b-e2ec-4cf3-bc74-088d10943f45
Kurukulaaratchy, Ramesh J.
535e7160-a74e-463e-8acf-3491d6311bb2
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Ewart, Susan L.
48158071-d7b8-46b5-8aef-26ffb37eec3b
Arshad, S. Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Erlewyn-Lajeunesse, Mich
5c04ba04-f1fd-4634-a09e-38ecc993e1be
Venkataraman, Devasmitha
5d80518f-95d4-4872-8af7-095d77e1121b
Soto-Ramírez, Nelís
3526295b-e2ec-4cf3-bc74-088d10943f45
Kurukulaaratchy, Ramesh J.
535e7160-a74e-463e-8acf-3491d6311bb2
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Ewart, Susan L.
48158071-d7b8-46b5-8aef-26ffb37eec3b
Arshad, S. Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Erlewyn-Lajeunesse, Mich
5c04ba04-f1fd-4634-a09e-38ecc993e1be

Venkataraman, Devasmitha, Soto-Ramírez, Nelís, Kurukulaaratchy, Ramesh J., Holloway, John W., Karmaus, Wilfried, Ewart, Susan L., Arshad, S. Hasan and Erlewyn-Lajeunesse, Mich (2014) Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence. Journal of Allergy and Clinical Immunology, 134 (4), 876-882.e4. (doi:10.1016/j.jaci.2014.07.033). (PMID:25174864)

Record type: Article

Abstract

Background

Filaggrin is an epidermal protein that has a role in skin barrier function. Filaggrin loss-of-function (FLG-LOF) mutations are a significant risk factor for eczema and atopy, but their association with food allergy (FA) is less clear.

Objective

We explored the longitudinal relationship between 3 common FLG-LOF mutations and FA using the Isle of Wight birth cohort.

Methods

FA diagnosis was based on recognized allergic reactions within 4 hours after exposure to known food allergens. Food allergen sensitization (FAS) was identified by using skin prick tests conducted between 1 and 18 years of age to a range of food allergens. Three FLG mutations were genotyped in 1150 (79%) of 1456 children. The temporal relationships between FA, FAS, and eczema in children with FLG mutations were explored by using path analysis with total, direct, and indirect effect models.

Results

There was a significant total effect of FLG-LOF mutations on the risk of FA in later childhood at the ages of 10 (odds ratio, 31.46; 95% CI, 2.86 to >100) and 18 (odds ratio, 4.25; 95% CI, 1.55-11.61) years. Path analysis showed that there was no direct effect of FLG-LOF mutations on FA at any age; however, an indirect effect was found on FA at all ages through eczema and FAS in the earlier years.

Conclusion

FLG-LOF mutations are associated with FA in older children through eczema and FAS during early childhood. Our results highlight a biologically plausible pathway, which suggests that skin barrier function is important in the development and persistence of FA.

Full text not available from this repository.

More information

Accepted/In Press date: 22 July 2014
e-pub ahead of print date: 28 August 2014
Published date: October 2014
Keywords: food allergy, filaggrin, FLG-LOF, food allergen sensitization, path analysis, prediction, eczema
Organisations: Human Development & Health, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 368537
URI: https://eprints.soton.ac.uk/id/eprint/368537
ISSN: 0091-6749
PURE UUID: 2d42260b-2c62-4e50-a0d9-02ffeb7e8434
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 02 Sep 2014 15:45
Last modified: 29 Aug 2019 00:50

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