Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum

Peisong Gao, Nicholas M. Rafaels, Tracey Hand, Tanda Murray, Mark Boguniewicz, Tissa Hata, Lynda Schneider, Jon M. Hanifin, Richard L. Gallo, Li Gao, Terri L Beaty, Lisa A. Beck, Kathleen C. Barnes, Donald Y M Leung

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Abstract

Background: Loss-of-function null mutations R501X and 2282del4 in the skin barrier gene, filaggrin (FLG), represent the most replicated genetic risk factors for atopic dermatitis (AD). Associations have not been reported in African ancestry populations. Atopic dermatitis eczema herpeticum (ADEH) is a rare but serious complication of AD resulting from disseminated cutaneous herpes simplex virus infections. Objective: We aimed to determine whether FLG polymorphisms contribute to ADEH susceptibility. Methods: Two common loss-of-function mutations plus 9 FLG single nucleotide polymorphisms were genotyped in 278 European American patients with AD, of whom 112 had ADEH, and 157 nonatopic controls. Replication was performed on 339 African American subjects. Results: Significant associations were observed for both the R501X and 2282del4 mutations and AD among European American subjects (P = 1.46 × 10-5, 3.87 × 10-5, respectively), but the frequency of the R501X mutation was 3 times higher (25% vs 9%) for ADEH than for AD without eczema herpeticum (EH) (odds ratio [OR], 3.4; 1.7-6.8; P = .0002). Associations with ADEH were stronger with the combined null mutations (OR, 10.1; 4.7-22.1; P = 1.99 × 10-11). Associations with the R501X mutation were replicated in the African American population; the null mutation was absent among healthy African American subjects, but present among patients with AD (3.2%; P = .035) and common among patients with ADEH (9.4%; P = .0049). However, the 2282del4 mutation was absent among African American patients with ADEH and rare (

Original languageEnglish (US)
JournalThe Journal of Allergy and Clinical Immunology
Volume124
Issue number3
DOIs
StatePublished - Sep 2009

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Keywords

  • 2282del4
  • Atopic dermatitis
  • eczema herpeticum
  • filaggrin
  • R501X
  • single nucleotide polymorphisms

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Gao, P., Rafaels, N. M., Hand, T., Murray, T., Boguniewicz, M., Hata, T., Schneider, L., Hanifin, J. M., Gallo, R. L., Gao, L., Beaty, T. L., Beck, L. A., Barnes, K. C., & Leung, D. Y. M. (2009). Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum. The Journal of Allergy and Clinical Immunology, 124(3). https://doi.org/10.1016/j.jaci.2009.07.034