Dataset Information

Common FLG mutation K4671X not associated with atopic dermatitis in Han Chinese in a family association study.

ABSTRACT:

Background

Filaggrin gene (FLG) mutations have been identified as the cause of ichthyosis vulgaris (IV) and major predisposing factors for atopic dermatitis (AD). The relationship among AD, IV and FLG mutations has not been clarified yet. Mutations 3321delA and K4671X, two of the most common mutations in Chinese patients, were both statistically associated with AD in case-control studies.

Materials and methods

A group of 100 family trios (a total of 300 members with one affected AD proband and both parents) were recruited and screened for three filaggrin null mutations (3222del4, 3321delA and K4671X). The subjects' manifestations of AD and IV were assessed by two experienced dermatologists and recorded in detail. The relationship of common mutations to AD were assessed using both case-control and family-based tests of association. Filaggrin expression was measured in skin of 3 subjects with K4671X heterozygote and the normal control using quantitative real-time RT-PCR and immunohistochemistry.

Results

Of 100 probands for AD, 22 were carriers for common FLG mutations and only 2 of them were from 40 none-IV family trios (5.00%), consistent with that of the healthy control group (3.99%, P>0.05). Significant statistical associations were revealed between AD and 3321delA (P<0.001, odds ratio 12.28, 95% confidence interval 3.35-44.98) as well as K4671X (P?=?0.002, odds ratio 4.53, 95% confidence interval 1.77-11.60). The family-based approach revealed that 3321delA was over-transmitted to AD offspring from parents (T:U?=?12?1, P?=?0.003) but failed to demonstrate transmission disequilibrium between K4671X and AD (T:U?=?10?8, P?=?0.815). Moreover, compared to the normal control, filaggrin expression at both mRNA and protein levels in epidermis of subjects with K4671X(heter) was not reduced.

Conclusions

AD patients from none-IV family trios have low probability of carrying FLG mutations. The present family samples confirmed the susceptibility of mutation 3321delA to AD in Han Chinese. K4671X was not a pathogenic mutation.

SUBMITTER: Cheng R

PROVIDER: S-EPMC3496733 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Common FLG mutation K4671X not associated with atopic dermatitis in Han Chinese in a family association study.

Cheng Ruhong R Li Ming M Zhang Hui H Guo Yifeng Y Chen Xilan X Tao Jianfeng J Jiang Aifang A Gan Jiecheng J Qi Huaishan H Yu Hong H Liao Wanqing W Yao Zhirong Z

PloS one 20121113 11

<h4>Background</h4>Filaggrin gene (FLG) mutations have been identified as the cause of ichthyosis vulgaris (IV) and major predisposing factors for atopic dermatitis (AD). The relationship among AD, IV and FLG mutations has not been clarified yet. Mutations 3321delA and K4671X, two of the most common mutations in Chinese patients, were both statistically associated with AD in case-control studies.<h4>Materials and methods</h4>A group of 100 family trios (a total of 300 members with one affected A ...[more]

PMID: 23152869

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Project description:Summary Background: While patients and families struggling with atopic dermatitis (AD) have documented concerns for a contributory role of skin care products in AD pathology, nearly all the skin microbiome studies to date have asked participants to avoid topical products (such as soaps or select medications) for the preceding days to weeks prior to sample collection. Thus, given the established role of the microbiome in AD, the interactions between topical exposures, dysbiosis and AD remains underrepresented in the academic literature. Objectives: To address this knowledge gap, we expanded our previous evaluations to test the toxicological effects of a broader range of common chemicals, AD treatment lotions, creams and ointments using both health- and AD-associated strains of Roseomonas mucosa and Staphylococcus spp. Methods: Use of in vitro culture techniques and mouse models were deployed to identify chemicals with dysbiotic or pre-biotic potential. A proof-of-concept study was subsequently performed in healthy volunteers to assess global microbiome shifts after exposure to select chemicals using dermatologic patch testing. Results: Numerous chemicals possessed antibiotic properties, including many not marketed as anti-microbials. Through targeted combination of potentially beneficial chemicals, we identified combinations which promoted the growth of health-associated isolates over disease-associated strains in bacterial culture and enhanced microbe-specific outcomes in an established mouse model of AD; the most promising of which was the combination of citral and colophonium (often sold as lemon myrtle oil and pine tar). Additional studies would likely further optimize the combination of ingredients use. Similar results were seen in the proof-of-concept human studies. Conclusions: Our results could offer a systematic, multiplex approach to identify which products carry dysbiotic potential and thus may guide formulation of new topicals to benefit patients with AD.

Dataset Information

Common FLG mutation K4671X not associated with atopic dermatitis in Han Chinese in a family association study.

Background

Materials and methods

Results

Conclusions

Publications

Common FLG mutation K4671X not associated with atopic dermatitis in Han Chinese in a family association study.

Similar Datasets

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