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Filaggrin gene loss‐of‐function mutations constitute a factor in patients with multiple contact allergies
Author(s) -
Elhaji Youssef,
Sasseville Denis,
Pratt Melanie,
Asai Yuka,
Matheson Kara,
McLean William H. I.,
Hull Peter R.
Publication year - 2019
Publication title -
contact dermatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.524
H-Index - 96
eISSN - 1600-0536
pISSN - 0105-1873
DOI - 10.1111/cod.13268
Subject(s) - filaggrin , medicine , loss function , atopic dermatitis , patch test , dermatology , allergy , contact dermatitis , mutation , immunology , gene , genetics , biology , phenotype
Background Polysensitivity is defined as three or more positive patch test reactions. The role of filaggrin gene ( FLG ) loss‐of‐function mutations in patients with polysensitivity has not been studied when barrier bypass and possible preceding barrier damage have been excluded. Objectives To determine whether FLG loss of function mutations play a role in patients with multiple contact sensitivities when barrier bypass is excluded. Methods One hundred and sixty‐nine patients with three or more, non‐cross‐reacting, positive patch test reactions were prospectively enrolled in this study. Exclusion criteria were a history of hand dermatitis, nickel and metal implants, and stasis dermatitis. Subjects were patch tested with the North American extended patch test series, and with other relevant haptens. DNA was obtained and sequenced for the following FLG loss‐of‐function mutations: R501X, 2282del4, R2447X, and S3247X. Results One hundred and sixty‐five patients were genotyped for the four FLG mutations. There was a significant association between R501X mutation and polysensitivity. For the other three tested mutations, there were no significant associations with polysensitivity. When all mutations were combined, there was a significant association between loss‐of‐function FLG mutations and polysensitivity in patients with a history of atopic dermatitis. Conclusion When skin barrier bypass is excluded, there is a significant association between polysensitivity and FLG loss‐of‐function mutations.