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Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence - 02/10/14

Doi : 10.1016/j.jaci.2014.07.033 
Devasmitha Venkataraman, MD, MRCPCH, MSc a, b, Nelís Soto-Ramírez, MPH, MD c, Ramesh J. Kurukulaaratchy, DM, FRCP d, e, John W. Holloway, PhD f, g, Wilfried Karmaus, MD, Drmed, MPH c, Susan L. Ewart, PhD h, S. Hasan Arshad, FRCP, DM d, e, f, , Mich Erlewyn-Lajeunesse, FRCPCH, DM e, f
a University of Southampton, Faculty of Medicine, Southampton, United Kingdom 
b James Cook University Hospital, Middlesbrough, United Kingdom 
c Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, Tenn 
d David Hide Asthma and Allergy Research Centre, Isle of Wight, United Kingdom 
e University Hospitals Southampton NHS Foundation Trust, Southampton, United Kingdom 
f Clinical and Experimental Sciences, University of Southampton, Southampton, United Kingdom 
g Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom 
h College of Veterinary Medicine, Michigan State University, East Lansing, Mich 

Corresponding author: S. Hasan Arshad, FRCP, DM, The David Hide Asthma & Allergy Research Centre and University of Southampton, Clinical and Experimental Sciences, St Mary's Hospital, Newport, Isle of Wight PO30 5TG, United Kingdom.

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.

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Key words : Food allergy, filaggrin, FLG-LOF, food allergen sensitization, path analysis, prediction, eczema

Abbreviations used : FA, FAS, FLG, FLG-LOF, IOW, OR, SPT


Plan


 Supported by National Institutes of Health project grants R01-HL082925, R01-AI061471, and R01-AI091905. The 10-year follow-up of this study was funded by the National Asthma Campaign, UK (grant no. 364).
 Disclosure of potential conflict of interest: This study was funded by the National Institutes of Health. The authors declare that they have no other relevant conflicts of interest.


© 2014  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 134 - N° 4

P. 876 - octobre 2014 Retour au numéro
Article précédent Article précédent
  • Peanut allergy: Effect of environmental peanut exposure in children with filaggrin loss-of-function mutations
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