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Mutation Ups Risk of Atopy With Eczema Herpeticum


 

WASHINGTON — A filaggrin mutation appears to confer susceptibility to atopic dermatitis complicated by eczema herpeticum, study results showed.

In a genotyping study, single-locus association tests revealed that filaggrin R501X null mutation is significantly associated with atopic dermatitis (AD) and atopic dermatitis complicated with eczema herpeticum (ADEH) in white and black patients, Kathleen C. Barnes, Ph.D., said in a poster presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

"This study of filaggrin polymorphisms suggests the functional R501X mutation, in addition to AD risk, confers an added risk of ADEH, with an estimated effect size of nearly 12 [OR = 11.8] among [white] patients," the researchers wrote. Notably, this is the first study demonstrating an association between filaggrin polymorphisms and the risk of AD and associated traits in blacks, according to Dr. Barnes of the division of allergy and clinical immunology at Johns Hopkins University in Baltimore.

The study included 414 white patients with atopy (165 with AD, 93 with ADEH, and 156 nonatopic controls) and 328 black patients (155 with AD, 21 with ADEH, and 152 nonatopic controls). AD was diagnosed using the U.S. consensus criteria. ADEH was defined as AD with at least one documented episode of eczema herpeticum. Total serum IgE levels were measured and eczema severity was assessed using the eczema area and severity index grading system.

The R501X null mutation was genotyped using the TaqMan allelic discrimination assay. In addition, the 2282del4 mutation was genotyped using an ABI 3700 sequencer. Nine tagging single-nucleotide polymorphisms were genotyped.

The researchers found significant associations between the 2282del4 mutation and AD, with allele frequencies of 10.7% among all AD patients, compared with 5.6% among controls. However, no association was observed when the analysis was limited to the patients with ADEH. Also, no associations were observed between 2282del4 and AD or ADEH among blacks, likely because of the low frequency among healthy controls (less than 1%) and AD patients (6%) and the complete absence among ADEH patients.

"The relationship between this null mutation and disease might be related to an increased propensity to disseminated viral skin infections resulting from skin barrier dysfunction," the researchers speculated.

Dr. Barnes reported having no relevant financial relationships.

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