Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations

Stephan Weidinger; Thomas Illig; Hansjörg Baurecht; Alan D. Irvine; Elke Rodriguez; Amalia Diaz-Lacava; Norman Klopp; Stefan Wagenpfeil; Yiwei Zhao; Haihui Liao; Simon P. Lee; Colin N A Palmer; Claudia Jenneck; Laura Maintz; Tobias Hagemann; Heidrun Behrendt; Johannes Ring; Markus M. Nothen; W. H Irwin McLean; Natalija Novak

doi:10.1016/j.jaci.2006.05.004

Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations

Stephan Weidinger, Thomas Illig, Hansjörg Baurecht, Alan D. Irvine, Elke Rodriguez, Amalia Diaz-Lacava, Norman Klopp, Stefan Wagenpfeil, Yiwei Zhao, Haihui Liao, Simon P. Lee, Colin N A Palmer, Claudia Jenneck, Laura Maintz, Tobias Hagemann, Heidrun Behrendt, Johannes Ring, Markus M. Nothen, W. H Irwin McLean, Natalija Novak

Research output: Contribution to journal › Article › peer-review

536 Citations (Scopus)

Abstract

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a strong genetic background. One of the characteristic features of AD and causative factor for the disease is an impaired epidermal skin barrier based on a primary defect of epidermal differentiation.

Objectives: Recently, 2 loss-of-function mutations (R501X and 2282derl4) in the filaggrin gene (FLG) that cause ichthyosis vulgaris, one of the most common inherited skin disorders of keratinization, have been reported to be strong predisposing factors for AD.

Methods: We evaluated the association of the loss-of-function mutations R501X and 2282del4 within the FLG gene in a large collection of 476 well-characterized white German families with AD by using the transmission-disequilibrium test.

Results: Our family-based approach revealed prominent associations between the 2 loss-of-function FLG mutations and AD, as previously observed in a traditional Mendelian linkage analysis and case-control cohort analysis approach. In addition, we observed associations of the FLG mutations in particular with the extrinsic subtype of AD, which is characterized by high total serum IgE levels and concomitant allergic sensitizations. Furthermore, FLG mutations are significantly associated with palmar hyperlinearity in patients with AD, which represents a shared feature of AD and ichthyosis vulgaris.

Conclusion: Together these data implicate that FLG is the first really strong genetic factor identified in a common complex disease. Clinical implications: These findings underline the crucial role of the skin barrier in preventing allergic sensitization.

Original language	English
Pages (from-to)	214-219
Number of pages	6
Journal	Journal of Allergy and Clinical Immunology
Volume	118
Issue number	1
DOIs	https://doi.org/10.1016/j.jaci.2006.05.004
Publication status	Published - 1 Jul 2006

Keywords

Atopic dermatitis
epidermal differentiation complex
filaggrin
polymorphisms
skin barrier

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/j.jaci.2006.05.004

Cite this

Weidinger, S., Illig, T., Baurecht, H., Irvine, A. D., Rodriguez, E., Diaz-Lacava, A., Klopp, N., Wagenpfeil, S., Zhao, Y., Liao, H., Lee, S. P., Palmer, C. N. A., Jenneck, C., Maintz, L., Hagemann, T., Behrendt, H., Ring, J., Nothen, M. M., McLean, W. H. I., & Novak, N. (2006). Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. Journal of Allergy and Clinical Immunology, 118(1), 214-219. https://doi.org/10.1016/j.jaci.2006.05.004

@article{684bffc10b90439fbab02441f7268ab2,

title = "Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations",

abstract = "Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a strong genetic background. One of the characteristic features of AD and causative factor for the disease is an impaired epidermal skin barrier based on a primary defect of epidermal differentiation.Objectives: Recently, 2 loss-of-function mutations (R501X and 2282derl4) in the filaggrin gene (FLG) that cause ichthyosis vulgaris, one of the most common inherited skin disorders of keratinization, have been reported to be strong predisposing factors for AD.Methods: We evaluated the association of the loss-of-function mutations R501X and 2282del4 within the FLG gene in a large collection of 476 well-characterized white German families with AD by using the transmission-disequilibrium test.Results: Our family-based approach revealed prominent associations between the 2 loss-of-function FLG mutations and AD, as previously observed in a traditional Mendelian linkage analysis and case-control cohort analysis approach. In addition, we observed associations of the FLG mutations in particular with the extrinsic subtype of AD, which is characterized by high total serum IgE levels and concomitant allergic sensitizations. Furthermore, FLG mutations are significantly associated with palmar hyperlinearity in patients with AD, which represents a shared feature of AD and ichthyosis vulgaris.Conclusion: Together these data implicate that FLG is the first really strong genetic factor identified in a common complex disease. Clinical implications: These findings underline the crucial role of the skin barrier in preventing allergic sensitization.",

keywords = "Atopic dermatitis, epidermal differentiation complex, filaggrin, polymorphisms, skin barrier",

author = "Stephan Weidinger and Thomas Illig and Hansj{\"o}rg Baurecht and Irvine, {Alan D.} and Elke Rodriguez and Amalia Diaz-Lacava and Norman Klopp and Stefan Wagenpfeil and Yiwei Zhao and Haihui Liao and Lee, {Simon P.} and Palmer, {Colin N A} and Claudia Jenneck and Laura Maintz and Tobias Hagemann and Heidrun Behrendt and Johannes Ring and Nothen, {Markus M.} and McLean, {W. H Irwin} and Natalija Novak",

year = "2006",

month = jul,

day = "1",

doi = "10.1016/j.jaci.2006.05.004",

language = "English",

volume = "118",

pages = "214--219",

journal = "Journal of Allergy and Clinical Immunology",

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Weidinger, S, Illig, T, Baurecht, H, Irvine, AD, Rodriguez, E, Diaz-Lacava, A, Klopp, N, Wagenpfeil, S, Zhao, Y, Liao, H, Lee, SP, Palmer, CNA, Jenneck, C, Maintz, L, Hagemann, T, Behrendt, H, Ring, J, Nothen, MM, McLean, WHI & Novak, N 2006, 'Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations', Journal of Allergy and Clinical Immunology, vol. 118, no. 1, pp. 214-219. https://doi.org/10.1016/j.jaci.2006.05.004

TY - JOUR

T1 - Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations

AU - Weidinger, Stephan

AU - Illig, Thomas

AU - Baurecht, Hansjörg

AU - Irvine, Alan D.

AU - Rodriguez, Elke

AU - Diaz-Lacava, Amalia

AU - Klopp, Norman

AU - Wagenpfeil, Stefan

AU - Zhao, Yiwei

AU - Liao, Haihui

AU - Lee, Simon P.

AU - Palmer, Colin N A

AU - Jenneck, Claudia

AU - Maintz, Laura

AU - Hagemann, Tobias

AU - Behrendt, Heidrun

AU - Ring, Johannes

AU - Nothen, Markus M.

AU - McLean, W. H Irwin

AU - Novak, Natalija

PY - 2006/7/1

Y1 - 2006/7/1

N2 - Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a strong genetic background. One of the characteristic features of AD and causative factor for the disease is an impaired epidermal skin barrier based on a primary defect of epidermal differentiation.Objectives: Recently, 2 loss-of-function mutations (R501X and 2282derl4) in the filaggrin gene (FLG) that cause ichthyosis vulgaris, one of the most common inherited skin disorders of keratinization, have been reported to be strong predisposing factors for AD.Methods: We evaluated the association of the loss-of-function mutations R501X and 2282del4 within the FLG gene in a large collection of 476 well-characterized white German families with AD by using the transmission-disequilibrium test.Results: Our family-based approach revealed prominent associations between the 2 loss-of-function FLG mutations and AD, as previously observed in a traditional Mendelian linkage analysis and case-control cohort analysis approach. In addition, we observed associations of the FLG mutations in particular with the extrinsic subtype of AD, which is characterized by high total serum IgE levels and concomitant allergic sensitizations. Furthermore, FLG mutations are significantly associated with palmar hyperlinearity in patients with AD, which represents a shared feature of AD and ichthyosis vulgaris.Conclusion: Together these data implicate that FLG is the first really strong genetic factor identified in a common complex disease. Clinical implications: These findings underline the crucial role of the skin barrier in preventing allergic sensitization.

AB - Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a strong genetic background. One of the characteristic features of AD and causative factor for the disease is an impaired epidermal skin barrier based on a primary defect of epidermal differentiation.Objectives: Recently, 2 loss-of-function mutations (R501X and 2282derl4) in the filaggrin gene (FLG) that cause ichthyosis vulgaris, one of the most common inherited skin disorders of keratinization, have been reported to be strong predisposing factors for AD.Methods: We evaluated the association of the loss-of-function mutations R501X and 2282del4 within the FLG gene in a large collection of 476 well-characterized white German families with AD by using the transmission-disequilibrium test.Results: Our family-based approach revealed prominent associations between the 2 loss-of-function FLG mutations and AD, as previously observed in a traditional Mendelian linkage analysis and case-control cohort analysis approach. In addition, we observed associations of the FLG mutations in particular with the extrinsic subtype of AD, which is characterized by high total serum IgE levels and concomitant allergic sensitizations. Furthermore, FLG mutations are significantly associated with palmar hyperlinearity in patients with AD, which represents a shared feature of AD and ichthyosis vulgaris.Conclusion: Together these data implicate that FLG is the first really strong genetic factor identified in a common complex disease. Clinical implications: These findings underline the crucial role of the skin barrier in preventing allergic sensitization.

KW - Atopic dermatitis

KW - epidermal differentiation complex

KW - filaggrin

KW - polymorphisms

KW - skin barrier

U2 - 10.1016/j.jaci.2006.05.004

DO - 10.1016/j.jaci.2006.05.004

M3 - Article

C2 - 16815158

AN - SCOPUS:33745353511

SN - 0091-6749

VL - 118

SP - 214

EP - 219

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 1

ER -

Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations

Abstract

Keywords

ASJC Scopus subject areas

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