Atopic dermatitis and skin diseaseFilaggrin null mutations and childhood atopic eczema: A population-based case-control study
Section snippets
Study design and case definition
We used a population cohort (n = 7737) from the northwest of England for whom DNA samples had been collected at birth,21 representing more than 85% of all deliveries in one hospital (West Cumberland Hospital, Whitehaven) between 1996 and 2003. This geographic area is particularly useful for epidemiologic research because of the relatively low rates of population movement. Children within the birth cohort catchment region who had not previously been included in the cohort were offered the
Results
Seventy-five percent (43/57) of eligible schools agreed to take part in the research by distributing study literature and facilitating skin examinations by the visiting dermatologist. An estimated 3086 children in these schools were within the target age range, and consent to participate was given by the parents/guardians of 811 (26%) children. Eight hundred one questionnaires were completed, 792 children underwent skin examination, and 805 DNA samples were located from the birth cohort stores
Discussion
There have, to date, been no published studies investigating the role of FLG mutations in the mild-to-moderate eczema that predominates in our society. We used a unique resource in the northwest of England, an unselected birth cohort with DNA samples, to investigate this question. We were careful to define eczema using a well-validated method (the UK modification of Hanifin and Rajka's diagnostic criteria)26 in addition to skin examination by an experienced dermatologist. This allowed us to
References (37)
- et al.
Revised nomenclature for allergy for global use: report of the Nomenclature Review Committee of the World Allergy Organization, October 2003
J Allergy Clin Immunol
(2004) - et al.
Development of the Childhood Atopic Dermatitis Impact Scale: initial validation of a quality-of-life measure for young children with atopic dermatitis and their families
J Invest Dermatol
(2005) - et al.
The atopic march: the pattern of allergic disease development in childhood
Immunol Allergy Clin North Am
(2005) - et al.
Interaction of filaggrin with keratin filaments during advanced stages of normal human epidermal differentiation and in ichthyosis vulgaris
Differentiation
(1991) Fleshing out filaggrin phenotypes
J Invest Dermatol
(2007)- et al.
Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations
J Allergy Clin Immunol
(2006) - et al.
Filaggrin loss-of-function mutations predispose to phenotypes involved in the atopic march
J Allergy Clin Immunol
(2006) - et al.
Null mutations in the filaggrin gene (FLG) determine major susceptibility to early-onset atopic dermatitis that persists into adulthood
J Invest Dermatol
(2007) - et al.
Two common loss-of-function mutations within the filaggrin gene predispose for early onset of atopic dermatitis
J Invest Dermatol
(2007) - et al.
Filaggrin mutations strongly predispose to early-onset and extrinsic atopic dermatitis
J Invest Dermatol
(2007)
Filaggrin mutations in children with severe atopic dermatitis
J Invest Dermatol
The prevalence of childhood atopic eczema in a general population
J Am Acad Dermatol
Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report
J Allergy Clin Immunol
The natural course of atopic dermatitis from birth to age 7 years and the association with asthma
J Allergy Clin Immunol
Prevalent and rare mutations in the gene encoding filaggrin cause ichthyosis vulgaris and predispose individuals to atopic dermatitis
J Invest Dermatol
Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis
J Allergy Clin Immunol
Skin barrier function and allergic risk
Nat Genet
Proceedings of the 4th Georg Rajka International Symposium on Atopic Dermatitis, Arcachon, France, September 15-17, 2005
J Allergy Clin Immunol
Cited by (0)
Supported by Newcastle Healthcare Charity, the British Skin Foundation, and Action Medical Research. S.J.B. is supported by the Lily Ross Fellowship and a British Society for Paediatric Dermatology training fellowship. Support for H.J.C. and partial support for S.J.B. is provided by a Senior Fellowship in Basic Biomedical Science (grant ref 074524) from the Wellcome Trust. Filaggrin research in the McLean laboratory is supported by grants from the British Skin Foundation, the National Eczema Society, and the Medical Research Council (reference no. G0700314) and by donations from anonymous families affected by eczema in the Tayside Region of Scotland.
Disclosure of potential conflict of interest: S. J. Brown has received research support from the Wellcome Trust, the British Skin Foundation, the British Society for Pediatric Dermatology, Newcastle Healthcare Charity, and Action Medical Research. C. L. Relton has received research support from Newcastle Healthcare Charity, European Union FP6, and the March of Dimes. N. J. Reynolds has received research support from Steifel UK and has legally consulted through Newcastle University. W. H. Irwin McLean has received research support from Debra UK and the Medical Research Council. H. J. Cordell has received research support from the Wellcome Trust, the Medical Research Council, Newcastle Healthcare Charity, and Action Medical Research. The rest of the authors have declared that they have no conflict of interest.