Atopic dermatitis and skin disease
Filaggrin null mutations and childhood atopic eczema: A population-based case-control study

https://doi.org/10.1016/j.jaci.2008.01.013Get rights and content

Background

Null mutations within the filaggrin gene (FLG) are associated with moderate-to-severe atopic eczema; their role in mild-to-moderate eczema in the general population is unknown.

Objective

We sought to investigate the significance of 5 common FLG null mutations in childhood atopic eczema in an unselected population cohort.

Methods

Eight hundred eleven English children aged 7 to 9 years were screened for FLG mutations. Eczema cases were defined by using United Kingdom diagnostic criteria and skin examination. Asthma and seasonal rhinitis cases were defined by parental questionnaire. Association between phenotype and genotype was investigated using Fisher exact test and logistic regression analysis.

Results

The 12-month period prevalence of atopic eczema was 24.2% (95% CI, 21.2% to 27.2%), with 96% (115/120) of cases having mild-to-moderate disease. The combined null genotype (carriage of ≥1 FLG mutations) was significantly associated with atopic eczema (P = 1.2 × 10−4). The odds ratio (OR) for individuals carrying 2 null mutations was 26.9 (95% CI, 3.3-217.1), but heterozygote carriers showed no significant increase in risk (OR, 1.2; 95% CI, 0.7-1.9). Eight of 190 eczema cases (4.2%) carried 2 FLG null mutations and thus might be attributed to filaggrin deficiency. Asthma in the context of eczema showed significant association with the FLG null mutations (P = 7.1 × 10−4). There was no association of FLG with asthma independent of eczema (P = .15) and no association with seasonal rhinitis (P = .66).

Conclusion

FLG null mutations are significantly associated with mild-to-moderate atopic eczema in childhood, with a recessive pattern of inheritance.

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

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  • 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.

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