Filaggrin null mutations and childhood atopic eczema: A population-based case-control study - 15/08/11
, Caroline L. Relton, PhD c, Haihui Liao, MD d, Yiwei Zhao, MD d, Aileen Sandilands, PhD d, Ian J. Wilson, PhD b, John Burn, MD b, Nick J. Reynolds, MD a, e, W. H. Irwin McLean, PhD, DSc d, Heather J. Cordell, DPhil b
Reprint requests: Sara J. Brown, MRCP, Institute of Human Genetics, International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, United Kingdom.Abstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, seasonal rhinitis, atopic eczema, complex trait, filaggrin, ichthyosis vulgaris, skin barrier function
Abbreviations used : FLG, OR, UK
Plan
| 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. |
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| 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. |
Vol 121 - N° 4
P. 940 - avril 2008 Retour au numéro
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