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The association between null mutations in the filaggrin gene and contact sensitization to nickel and other chemicals in the general population

Authors

  • J.P. Thyssen,

    1. National Allergy Research Centre, Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, University of Copenhagen, Niels Andersens Vej 65, 2900 Hellerup, Denmark
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  • J.D. Johansen,

    1. National Allergy Research Centre, Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, University of Copenhagen, Niels Andersens Vej 65, 2900 Hellerup, Denmark
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  • A. Linneberg,

    1. Research Centre for Prevention and Health, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark
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  • T. Menné,

    1. National Allergy Research Centre, Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, University of Copenhagen, Niels Andersens Vej 65, 2900 Hellerup, Denmark
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  • N.H. Nielsen,

    1. Dermatology Clinic, Bagsværd, Denmark
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  • M. Meldgaard,

    1. Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
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  • P.B. Szecsi,

    1. Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
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  • S. Stender,

    1. Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
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  • B.C. Carlsen

    1. National Allergy Research Centre, Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, University of Copenhagen, Niels Andersens Vej 65, 2900 Hellerup, Denmark
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  • Conflicts of interests
    None declared.

Jacob Pontoppidan Thyssen.
E-mail: jacpth01@geh.regionh.dk

Summary

Background  It was recently shown that filaggrin gene (FLG) null mutations are positively associated with nickel sensitization. We have hypothesized that histidine-rich filaggrin proteins in the epidermis chelate nickel ions and prevent their skin penetration and exposure to Langerhans cells. Furthermore, we have proposed that the low degree of genetic predisposition to nickel sensitization found by a Danish twin study was explained by a high prevalence of ear piercing among participants resulting in ‘bypassing’ of the filaggrin proteins.

Objectives  To investigate the association between FLG null mutations and (nickel) contact sensitization.

Methods  A random sample of 3335 adults from the general population in Denmark was patch tested and genotyped for R501X and 2282del4 in the FLG gene.

Results  The combined carrier frequency of FLG null mutations was 8·1%. Nickel, fragrance and contact sensitization to at least one allergen were not associated with FLG null mutations. A crude analysis on women who did not have ear piercings revealed a positive association between FLG null mutations and nickel sensitization [8·3% vs. 2·4%; odds ratio (OR) 3·71, 95% confidence interval (CI) 0·73–18·96] as well as between FLG null mutations and allergic nickel dermatitis (8·3% vs. 1·3%; OR 6·75, 95% CI 1·17–38·91). FLG mutation status and atopic dermatitis were positively associated with neomycin or ethylenediamine sensitization.

Conclusions  This study suggests that FLG null mutations may be a risk factor for the development of nickel sensitization. However, ear piercing was a much stronger risk factor in our general population and we could therefore identify a positive association only in women without ear piercings. Contact sensitization to specific chemicals is related to treatment exposure.

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