Chromosome 11q13.5 variant associated with childhood eczema: An effect supplementary to filaggrin mutations

Background Atopic eczema is a common inflammatory skin disease with multifactorial etiology. The genetic basis is incompletely understood; however, loss of function mutations in the filaggrin gene (FLG) are the most significant and widely replicated genetic risk factor reported to date. The first ge...

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Bibliographic Details
Published in:Journal of allergy and clinical immunology 2010, Vol.125 (1), p.170-174.e2
Main Authors: O'Regan, Gráinne M., MB, Campbell, Linda E., BSc, Cordell, Heather J., DPhil, Irvine, Alan D., MD, McLean, W.H. Irwin, DSc, FRSE, FMedSci, Brown, Sara J., MD
Format: Article
Language:English
Subjects:
Adolescent
Adult
Allergic diseases
Allergy
Allergy and Immunology
atopic dermatitis
Atopic Dermatitis and Skin Disease
Atopy
Biological and medical sciences
Case-Control Studies
Child
Child, Preschool
Children
Children & youth
chromosome 11
Chromosomes
Chromosomes, Human, Pair 11 - genetics
Dermatitis, Atopic - genetics
Eczema
Female
Filaggrin
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Gene mapping
Genetic Predisposition to Disease
Genetic Variation
Genome-Wide Association Study
Humans
Immunopathology
inflammatory skin disease
Intermediate Filament Proteins - genetics
Ireland
Logistics
Male
Mapping
Medical sciences
Middle Aged
Mutation
Pediatrics
Polymorphism, Single Nucleotide
Population
Regression analysis
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
Single-nucleotide polymorphism
Skin allergic diseases. Stinging insect allergies
skin barrier
Studies
Susceptibility
Variables
Young Adult
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Summary:Background Atopic eczema is a common inflammatory skin disease with multifactorial etiology. The genetic basis is incompletely understood; however, loss of function mutations in the filaggrin gene (FLG) are the most significant and widely replicated genetic risk factor reported to date. The first genome-wide association study in atopic eczema recently identified 2 novel genetic variants in association with eczema susceptibility: a single nucleotide polymorphism on chromosome 11q13.5 (rs7927894) and a single nucleotide polymorphism (rs877776) within the gene encoding hornerin on chromosome 1q21. Objective To test the association of these 2 novel variants with pediatric eczema and to investigate their interaction with FLG null mutations. Methods Case-control study to investigate the association of rs7927894, rs877776 and the 4 most prevalent FLG null mutations with moderate-severe eczema in 511 Irish pediatric cases and 1000 Irish controls. Comprehensive testing for interaction between each of the loci was also performed. Results The association between rs7927894 and atopic eczema was replicated in this population ( P = .0025, χ2 test; odds ratio, 1.27; 95% CI, 1.09-1.49). The 4 most common FLG null variants were strongly associated with atopic eczema ( P = 1.26 × 10−50 ; combined odds ratio, 5.81; 95% CI, 4.51-7.49). Interestingly, the rs7927894 association was independent of the well-established FLG risk alleles and may be multiplicative in its effect. There was no significant association between rs877776 and pediatric eczema in this study. Conclusion Single nucleotide polymorphism rs7927894 appears to mark a genuine eczema susceptibility locus that will require further elucidation through fine mapping and functional analysis.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2009.10.046