Filaggrin mutations are strongly associated with contact sensitization in individuals with dermatitis.
BACKGROUND
Although heterozygous filaggrin gene (FLG) mutation carriers seem to have an increased risk of atopic, irritant and allergic nickel dermatitis, it remains unclear whether the risk of contact sensitization to allergens other than nickel is also elevated in FLG mutation carriers.


OBJECTIVE
We hypothesized that heterozygous FLG mutation carriers who suffer from dermatitis will have strongly reduced or even absent filaggrin levels during episodes of inflammation, potentially increasing the penetration of contact allergens, and hence the risk of becoming sensitized.


METHODS
During 2006-2008, 3335 randomly invited 18-69-year-old adult Danes participated in a general health examination, filled out a questionnaire, and were genotyped for the R501X and 2282del4 mutations in FLG.


RESULTS
A logistic regression analysis restricted to individuals who reported atopic dermatitis and frequent episodes of hand eczema showed a strong association between FLG mutations and contact sensitization to allergens other than nickel (odds ratio 5.71; 95% confidence interval 1.31-24.94). In participants without dermatitis, no association was found between contact sensitization and FLG mutations.


CONCLUSIONS
FLG mutation carriers with self-reported dermatitis have an increased risk of contact sensitization to substances other than nickel, whereas FLG mutations alone may not, or may only slightly, increase the risk of sensitization.
Department of Dermato-Allergology, National Allergy Research Centre, Copenhagen University Hospital Gentofte, 2900 Hellerup, Denmark. jacob.p.thyssen@regionh.dk
Jacob P
JP
Thyssen
Allan
A
Linneberg
Katrine
K
Ross-Hansen
Berit C
BC
Carlsen
Michael
M
Meldgaard
Pal B
PB
Szecsi
Steen
S
Stender
Torkil
T
Menné
Jeanne D
JD
Johansen
D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D003876:Dermatitis, Atopic / Q000235:genetics*; D003877:Dermatitis, Contact / Q000235:genetics*; D017453:Dermatitis, Irritant / Q000235:genetics*; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010328:Patch Tests / Q000379:methods; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins