Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence
Devasmitha Venkataraman,Devasmitha Venkataraman,Nelís Soto-Ramírez,Ramesh Kurukulaaratchy,John W. Holloway,Wilfried Karmaus,Susan Ewart,S. Hasan Arshad,Mich Erlewyn-Lajeunesse +8 more
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FLG-LOF mutations are associated with FA in older children through eczema and FAS during early childhood, which suggests that skin barrier function is important in the development and persistence of FA.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.read more
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References
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Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis
Colin N. A. Palmer,Alan D. Irvine,Ana Terron-Kwiatkowski,Yiwei Zhao,Haihui Liao,Simon P. Lee,David Goudie,Aileen Sandilands,Linda E. Campbell,Frances J.D. Smith,Grainne M. O'Regan,Rosemarie Watson,Jo E Cecil,Sherri J. Bale,John G. Compton,John J. DiGiovanna,John J. DiGiovanna,Philip Fleckman,Sue Lewis-Jones,Gehan Arseculeratne,Ann Sergeant,Colin S. Munro,Brahim El Houate,Ken McElreavey,Liselotte Brydensholt Halkjaer,Hans Bisgaard,Somnath Mukhopadhyay,Somnath Mukhopadhyay,W.H. Irwin McLean +28 more
TL;DR: It is shown that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis.
Journal ArticleDOI
Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris
Frances J.D. Smith,Alan D. Irvine,Ana Terron-Kwiatkowski,Aileen Sandilands,Linda E. Campbell,Yiwei Zhao,Haihui Liao,Alan Evans,David Goudie,Sue Lewis-Jones,Gehan Arseculeratne,Colin S. Munro,Ann Sergeant,Grainne M. O'Regan,Sherri J. Bale,John G. Compton,John J. DiGiovanna,John J. DiGiovanna,Richard B. Presland,Philip Fleckman,W.H. Irwin McLean +20 more
TL;DR: It is found that loss or reduction of this major structural protein, filaggrin, leads to varying degrees of impaired keratinization.
Journal ArticleDOI
Factors Associated with the Development of Peanut Allergy in Childhood
TL;DR: Data from the Avon Longitudinal Study of Parents and Children is used to identify those with a convincing history of peanut allergy and the subgroup that reacted to a double-blind peanut challenge, which could lead to new strategies to prevent sensitization in infants who are at risk for subsequent peanut allergy.
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