Chromosome 11q13.5 variant associated with childhood eczema: an effect supplementary to filaggrin mutations.
J Allergy Clin Immunol
; 125(1): 170-4.e1-2, 2010 Jan.
Article
en En
| MEDLINE
| ID: mdl-20109745
ABSTRACT
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, chi(2) 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 x 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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Variación Genética
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Cromosomas Humanos Par 11
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Predisposición Genética a la Enfermedad
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Dermatitis Atópica
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Proteínas de Filamentos Intermediarios
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Mutación
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Irlanda