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

Hdl Handle:
http://hdl.handle.net/10147/207388
Title:
Chromosome 11q13.5 variant associated with childhood eczema: an effect supplementary to filaggrin mutations.
Authors:
O'Regan, Grainne M; Campbell, Linda E; Cordell, Heather J; Irvine, Alan D; McLean, W H Irwin; Brown, Sara J
Affiliation:
Department of Paediatric Dermatology, Our Lady's Children's Hospital, Crumlin,, Dublin, Ireland.
Citation:
J Allergy Clin Immunol. 2010 Jan;125(1):170-4.e1-2.
Journal:
The Journal of allergy and clinical immunology
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207388
DOI:
10.1016/j.jaci.2009.10.046
PubMed ID:
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.
Language:
eng
MeSH:
Adolescent; Adult; Case-Control Studies; Child; Child, Preschool; Chromosomes, Human, Pair 11/*genetics; Dermatitis, Atopic/*genetics; Female; *Genetic Predisposition to Disease; *Genetic Variation; Genome-Wide Association Study; Humans; Intermediate Filament Proteins/*genetics; Ireland; Male; Middle Aged; *Mutation; Polymorphism, Single Nucleotide; Young Adult
ISSN:
1097-6825 (Electronic); 0091-6749 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorO'Regan, Grainne Men_GB
dc.contributor.authorCampbell, Linda Een_GB
dc.contributor.authorCordell, Heather Jen_GB
dc.contributor.authorIrvine, Alan Den_GB
dc.contributor.authorMcLean, W H Irwinen_GB
dc.contributor.authorBrown, Sara Jen_GB
dc.date.accessioned2012-02-01T10:23:44Z-
dc.date.available2012-02-01T10:23:44Z-
dc.date.issued2012-02-01T10:23:44Z-
dc.identifier.citationJ Allergy Clin Immunol. 2010 Jan;125(1):170-4.e1-2.en_GB
dc.identifier.issn1097-6825 (Electronic)en_GB
dc.identifier.issn0091-6749 (Linking)en_GB
dc.identifier.pmid20109745en_GB
dc.identifier.doi10.1016/j.jaci.2009.10.046en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207388-
dc.description.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.en_GB
dc.language.isoengen_GB
dc.subject.meshAdolescenten_GB
dc.subject.meshAdulten_GB
dc.subject.meshCase-Control Studiesen_GB
dc.subject.meshChilden_GB
dc.subject.meshChild, Preschoolen_GB
dc.subject.meshChromosomes, Human, Pair 11/*geneticsen_GB
dc.subject.meshDermatitis, Atopic/*geneticsen_GB
dc.subject.meshFemaleen_GB
dc.subject.mesh*Genetic Predisposition to Diseaseen_GB
dc.subject.mesh*Genetic Variationen_GB
dc.subject.meshGenome-Wide Association Studyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshIntermediate Filament Proteins/*geneticsen_GB
dc.subject.meshIrelanden_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.mesh*Mutationen_GB
dc.subject.meshPolymorphism, Single Nucleotideen_GB
dc.subject.meshYoung Adulten_GB
dc.titleChromosome 11q13.5 variant associated with childhood eczema: an effect supplementary to filaggrin mutations.en_GB
dc.contributor.departmentDepartment of Paediatric Dermatology, Our Lady's Children's Hospital, Crumlin,, Dublin, Ireland.en_GB
dc.identifier.journalThe Journal of allergy and clinical immunologyen_GB
dc.description.provinceLeinster-

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