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

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

Research output: Contribution to journalArticle

138 Citations (Scopus)

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)
JournalJournal of Allergy and Clinical Immunology
Volume124
Issue number3
DOIs
StatePublished - Sep 2009

Fingerprint

Kaposi Varicelliform Eruption
Atopic Dermatitis
Mutation
African Americans
filaggrin

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum. / Gao, Pei Song; Rafaels, Nicholas M.; Hand, Tracey; Murray, Tanda; Boguniewicz, Mark; Hata, Tissa; Schneider, Lynda; Hanifin, Jon; Gallo, Richard L.; Gao, Li; Beaty, Terri H.; Beck, Lisa A.; Barnes, Kathleen C.; Leung, Donald Y M.

In: Journal of Allergy and Clinical Immunology, Vol. 124, No. 3, 09.2009.

Research output: Contribution to journalArticle

Gao, PS, Rafaels, NM, Hand, T, Murray, T, Boguniewicz, M, Hata, T, Schneider, L, Hanifin, J, Gallo, RL, Gao, L, Beaty, TH, Beck, LA, Barnes, KC & Leung, DYM 2009, 'Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum', Journal of Allergy and Clinical Immunology, vol. 124, no. 3. https://doi.org/10.1016/j.jaci.2009.07.034
Gao, Pei Song ; Rafaels, Nicholas M. ; Hand, Tracey ; Murray, Tanda ; Boguniewicz, Mark ; Hata, Tissa ; Schneider, Lynda ; Hanifin, Jon ; Gallo, Richard L. ; Gao, Li ; Beaty, Terri H. ; Beck, Lisa A. ; Barnes, Kathleen C. ; Leung, Donald Y M. / Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum. In: Journal of Allergy and Clinical Immunology. 2009 ; Vol. 124, No. 3.
@article{5e0cdf3fa07d4a5a8c9d0880c495b576,
title = "Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum",
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 (",
keywords = "2282del4, Atopic dermatitis, eczema herpeticum, filaggrin, R501X, single nucleotide polymorphisms",
author = "Gao, {Pei Song} and Rafaels, {Nicholas M.} and Tracey Hand and Tanda Murray and Mark Boguniewicz and Tissa Hata and Lynda Schneider and Jon Hanifin and Gallo, {Richard L.} and Li Gao and Beaty, {Terri H.} and Beck, {Lisa A.} and Barnes, {Kathleen C.} and Leung, {Donald Y M}",
year = "2009",
month = "9",
doi = "10.1016/j.jaci.2009.07.034",
language = "English (US)",
volume = "124",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "3",

}

TY - JOUR

T1 - Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum

AU - Gao, Pei Song

AU - Rafaels, Nicholas M.

AU - Hand, Tracey

AU - Murray, Tanda

AU - Boguniewicz, Mark

AU - Hata, Tissa

AU - Schneider, Lynda

AU - Hanifin, Jon

AU - Gallo, Richard L.

AU - Gao, Li

AU - Beaty, Terri H.

AU - Beck, Lisa A.

AU - Barnes, Kathleen C.

AU - Leung, Donald Y M

PY - 2009/9

Y1 - 2009/9

N2 - 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 (

AB - 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 (

KW - 2282del4

KW - Atopic dermatitis

KW - eczema herpeticum

KW - filaggrin

KW - R501X

KW - single nucleotide polymorphisms

UR - http://www.scopus.com/inward/record.url?scp=69349102719&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69349102719&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2009.07.034

DO - 10.1016/j.jaci.2009.07.034

M3 - Article

C2 - 19733298

AN - SCOPUS:69349102719

VL - 124

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 3

ER -