Chromosome 11q13.5 variant associated with childhood eczema: an effect supplementary to filaggrin mutations.
AuthorsO'Regan, Grainne M
Campbell, Linda E
Cordell, Heather J
Irvine, Alan D
McLean, W H Irwin
Brown, Sara J
AffiliationDepartment of Paediatric Dermatology, Our Lady's Children's Hospital, Crumlin,, Dublin, Ireland.
Chromosomes, Human, Pair 11/*genetics
*Genetic Predisposition to Disease
Genome-Wide Association Study
Intermediate Filament Proteins/*genetics
Polymorphism, Single Nucleotide
MetadataShow full item record
CitationJ Allergy Clin Immunol. 2010 Jan;125(1):170-4.e1-2.
JournalThe Journal of allergy and clinical immunology
AbstractBACKGROUND: 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.
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