Null mutations in the filaggrin gene (FLG) determine major susceptibility to early-onset atopic dermatitis that persists into adulthood

Jonathan N.W.N. Barker; Colin N.A. Palmer; Yiwei Zhao; Haihui Liao; Peter R. Hull; Simon P. Lee; Michael H. Allen; Simon J. Meggitt; Nicholas J. Reynolds; Richard C. Trembath; W. H.Irwin McLean

doi:10.1038/sj.jid.5700587

Null mutations in the filaggrin gene (FLG) determine major susceptibility to early-onset atopic dermatitis that persists into adulthood

Jonathan N.W.N. Barker, Colin N.A. Palmer, Yiwei Zhao, Haihui Liao, Peter R. Hull, Simon P. Lee, Michael H. Allen, Simon J. Meggitt, Nicholas J. Reynolds, Richard C. Trembath, W. H.Irwin McLean

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285 Citations (Scopus)

Abstract

Atopic dermatitis (AD) is a common disease with a complex etiology in childhood and adult life. A significant proportion of childhood AD is transient, but in many cases it persists into adulthood. We have recently shown that null mutations in the filaggrin gene (FLG) are an important predisposing factor for childhood eczema and eczema-associated asthma, but persistence to adulthood has not been analyzed. Here we studied a cohort of adult patients with persistent AD, which had been present since early childhood. In this cohort, the combined allele frequency of the two common FLGnull variants was 0.270 (cf. population frequency 0.046). This represents an odds ratio of 7.7 with 95% confidence interval of 5.3-10.9 and a χ² P-value of 1.7^-53. Our data conclusively demonstrate that identification of FLGnull alleles is an indicator of a poor prognosis in AD, predisposing to a form of eczema that starts in early infancy and persists into adulthood. This study helps to further define the nature of the AD phenotype associated with FLG null alleles.

Original language	English
Pages (from-to)	564-567
Number of pages	4
Journal	Journal of Investigative Dermatology
Volume	127
Issue number	3
DOIs	https://doi.org/10.1038/sj.jid.5700587
Publication status	Published - Mar 2007
Externally published	Yes

Bibliographical note

Funding Information:
We thank the patients and their families for their participation, which made this research possible. We also thank Alan D. Irvine, Our Lady's Children's Hospital, Crumlin, Dublin, for critical reading of this paper and to Jayne Mcfarlane, Epithelial Genetics Group, for clerical assistance. The Barker group was supported by The British Skin Foundation (N.J.R. and J.N.B.) and The Wellcome Trust (R.C.T. and J.N.B.). The McLean group is supported by grants from The Dystrophic Epidermolysis Bullosa Research Association, The Pachyonychia Congenita Project, and The British Skin Foundation/National Eczema Society. The Palmer group is supported by the Biotechnology and Biological Sciences Research Council (award D13460), Scottish Enterprise Tayside and the Gannochy Trust, and the Scottish Executive Genetic Health Initiative.

ASJC Scopus Subject Areas

Biochemistry
Molecular Biology
Dermatology
Cell Biology

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Barker, J. N. W. N., Palmer, C. N. A., Zhao, Y., Liao, H., Hull, P. R., Lee, S. P., Allen, M. H., Meggitt, S. J., Reynolds, N. J., Trembath, R. C., & McLean, W. H. I. (2007). Null mutations in the filaggrin gene (FLG) determine major susceptibility to early-onset atopic dermatitis that persists into adulthood. Journal of Investigative Dermatology, 127(3), 564-567. https://doi.org/10.1038/sj.jid.5700587

Barker, JNWN, Palmer, CNA, Zhao, Y, Liao, H, Hull, PR, Lee, SP, Allen, MH, Meggitt, SJ, Reynolds, NJ, Trembath, RC & McLean, WHI 2007, 'Null mutations in the filaggrin gene (FLG) determine major susceptibility to early-onset atopic dermatitis that persists into adulthood', Journal of Investigative Dermatology, vol. 127, no. 3, pp. 564-567. https://doi.org/10.1038/sj.jid.5700587

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title = "Null mutations in the filaggrin gene (FLG) determine major susceptibility to early-onset atopic dermatitis that persists into adulthood",

abstract = "Atopic dermatitis (AD) is a common disease with a complex etiology in childhood and adult life. A significant proportion of childhood AD is transient, but in many cases it persists into adulthood. We have recently shown that null mutations in the filaggrin gene (FLG) are an important predisposing factor for childhood eczema and eczema-associated asthma, but persistence to adulthood has not been analyzed. Here we studied a cohort of adult patients with persistent AD, which had been present since early childhood. In this cohort, the combined allele frequency of the two common FLGnull variants was 0.270 (cf. population frequency 0.046). This represents an odds ratio of 7.7 with 95% confidence interval of 5.3-10.9 and a χ2 P-value of 1.7-53. Our data conclusively demonstrate that identification of FLGnull alleles is an indicator of a poor prognosis in AD, predisposing to a form of eczema that starts in early infancy and persists into adulthood. This study helps to further define the nature of the AD phenotype associated with FLG null alleles.",

author = "Barker, {Jonathan N.W.N.} and Palmer, {Colin N.A.} and Yiwei Zhao and Haihui Liao and Hull, {Peter R.} and Lee, {Simon P.} and Allen, {Michael H.} and Meggitt, {Simon J.} and Reynolds, {Nicholas J.} and Trembath, {Richard C.} and McLean, {W. H.Irwin}",

note = "Funding Information: We thank the patients and their families for their participation, which made this research possible. We also thank Alan D. Irvine, Our Lady's Children's Hospital, Crumlin, Dublin, for critical reading of this paper and to Jayne Mcfarlane, Epithelial Genetics Group, for clerical assistance. The Barker group was supported by The British Skin Foundation (N.J.R. and J.N.B.) and The Wellcome Trust (R.C.T. and J.N.B.). The McLean group is supported by grants from The Dystrophic Epidermolysis Bullosa Research Association, The Pachyonychia Congenita Project, and The British Skin Foundation/National Eczema Society. The Palmer group is supported by the Biotechnology and Biological Sciences Research Council (award D13460), Scottish Enterprise Tayside and the Gannochy Trust, and the Scottish Executive Genetic Health Initiative.",

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doi = "10.1038/sj.jid.5700587",

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AU - Barker, Jonathan N.W.N.

AU - Palmer, Colin N.A.

AU - Zhao, Yiwei

AU - Liao, Haihui

AU - Hull, Peter R.

AU - Lee, Simon P.

AU - Allen, Michael H.

AU - Meggitt, Simon J.

AU - Reynolds, Nicholas J.

AU - Trembath, Richard C.

AU - McLean, W. H.Irwin

N1 - Funding Information: We thank the patients and their families for their participation, which made this research possible. We also thank Alan D. Irvine, Our Lady's Children's Hospital, Crumlin, Dublin, for critical reading of this paper and to Jayne Mcfarlane, Epithelial Genetics Group, for clerical assistance. The Barker group was supported by The British Skin Foundation (N.J.R. and J.N.B.) and The Wellcome Trust (R.C.T. and J.N.B.). The McLean group is supported by grants from The Dystrophic Epidermolysis Bullosa Research Association, The Pachyonychia Congenita Project, and The British Skin Foundation/National Eczema Society. The Palmer group is supported by the Biotechnology and Biological Sciences Research Council (award D13460), Scottish Enterprise Tayside and the Gannochy Trust, and the Scottish Executive Genetic Health Initiative.

PY - 2007/3

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N2 - Atopic dermatitis (AD) is a common disease with a complex etiology in childhood and adult life. A significant proportion of childhood AD is transient, but in many cases it persists into adulthood. We have recently shown that null mutations in the filaggrin gene (FLG) are an important predisposing factor for childhood eczema and eczema-associated asthma, but persistence to adulthood has not been analyzed. Here we studied a cohort of adult patients with persistent AD, which had been present since early childhood. In this cohort, the combined allele frequency of the two common FLGnull variants was 0.270 (cf. population frequency 0.046). This represents an odds ratio of 7.7 with 95% confidence interval of 5.3-10.9 and a χ2 P-value of 1.7-53. Our data conclusively demonstrate that identification of FLGnull alleles is an indicator of a poor prognosis in AD, predisposing to a form of eczema that starts in early infancy and persists into adulthood. This study helps to further define the nature of the AD phenotype associated with FLG null alleles.

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Null mutations in the filaggrin gene (FLG) determine major susceptibility to early-onset atopic dermatitis that persists into adulthood

Abstract

Bibliographical note

ASJC Scopus Subject Areas

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