The Editors' choiceThe burden of disease associated with filaggrin mutations: A population-based, longitudinal birth cohort study
Section snippets
Participants
The ALSPAC is a longitudinal, population-based birth cohort study that recruited 14,541 pregnant women residing in Avon, United Kingdom, with expected dates of delivery between April 1, 1991, and December 31, 1992. There were 14,062 liveborn children. The study protocol has been described previously,6, 7 and further details are available on the ALSPAC Web site (http://www.alspac.bris.ac.uk). Ethical approval for all aspects of data collection was obtained from the ALSPAC Law and Ethics
Results
Each of these 2 mutations is known to have essentially identical biochemical consequences,1, 5 and in this study association scores and penetrance results for the primary phenotypes discussed are very similar for these 2 mutations (see Table E1, Table E2 in the Online Repository at www.jacionline.org); we present and analyze here the combined genotypic data. A summary of genotyping results along with a phenotypic profile of the cohort is given in Table I.
Discussion
Filaggrin is a highly abundant protein in the outermost layers of the epidermis, where it performs a critical cell-compaction process during the formation of the stratum corneum, the terminally differentiated cell layers responsible for skin barrier function.14 Decreased or absent FLG expression because of inheritance of loss-of-function mutations, which are surprisingly prevalent in white populations of European origin, leads to impaired barrier function, allowing the entry of antigens,
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The UK Medical Research Council, the Wellcome Trust, and the University of Bristol provide core support for the Avon Longitudinal Study of Parents and Children. Measurements of pulmonary function and bronchial responsiveness were supported by a grant from the UK Medical Research Council. This research was specifically funded by the Department of Paediatric Dermatology, Our Lady's Children's Hospital Crumlin, Dublin, and the genotyping was supported by a grant from Tenovus (Tayside) to C.P. and S.M. C.P. is supported by the Chief Scientists Office of the Scottish Executive Generation Scotland Initiative. The McLean laboratory is supported by grants from the British Skin Foundation/National Eczema Association, the Pachyonychia Congenita Project, the Dystrophic Epidermolysis Bullosa Research Association, the Medical Research Council (reference no. G0700314), and anonymous donations from atopic families in the Tayside region of Scotland.
Disclosure of potential conflict of interest: S. P. Lee has received research support from Tenovus Scotland. M. Pembrey has received research support from the Wellcome Trust. C. N. A. Palmer has received research support from Wyeth Pharmaceuticals, Scottish Executive, and the Wellcome Trust. W. H. I. McLean has filed patents on filaggrin. A. D. Irvine has received research support from the Children's Medical and Research Foundation and has served as an expert witness in occupational skin disease litigation. The rest of the authors have reported no conflict of interest.