The Role of Filaggrin in the Skin Barrier and Disease Development

Armengot‐Carbó, Miquel; Hernández‐Martín, Ángela; Torrelo, Antonio

doi:10.1016/j.adengl.2014.12.007

Cited by 30 publications

(30 citation statements)

References 99 publications

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“…This study builds on the evidence that filaggrin expression is modulated, regardless of FLG variants, in eczema patients compared to healthy controls . Such an observation further highlights the importance of this structural protein for the development of functional skin barrier and the pathogenesis of eczema . We demonstrated that the predictive value of FLG expression measured in UCB is slightly improved when FLG genetic variants were added to the prediction models (see Table , model 2 vs model 4 and model 6 vs model 8).…”

Section: Discussionsupporting

confidence: 60%

Expression of the filaggrin gene in umbilical cord blood predicts eczema risk in infancy: A birth cohort study

Ziyab

Ewart

Lockett

et al. 2017

Clin Experimental Allergy

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Background Filaggrin gene (FLG) expression, particularly in the skin, has been linked to the development of the skin barrier and is associated with eczema risk. However, knowledge as to whether FLG expression in umbilical cord blood (UCB) is associated with eczema development and prediction is lacking. Objective This study sought to assess whether FLG expression in UCB associates with and predicts the development of eczema in infancy. Methods Infants enrolled in a birth cohort study (n = 94) were assessed for eczema at ages 3−, 6−, and 12-months. Five probes measuring FLG transcripts expression in UCB were available from genome-wide gene expression profiling. FLG genetic variants R501X, 2282del4, and S3247X were genotyped. Associations were assessed using Poisson regression with robust variance estimation. Area under the curve (AUC), describing the discriminatory/predictive performance of fitted models, was estimated from logistic regression. Results Increased level of FLG expression measured by probe A_24_P51322 was associated with reduced risk of eczema during the first year of life (RR = 0.60, 95% CI: 0.38–0.95). In contrast, increased level of FLG antisense transcripts measured by probe A_21_P0014075 was associated with increased risk of eczema (RR = 2.02, 95% CI: 1.10–3.72). In prediction models including FLG expression, FLG genetic variants, and sex, discrimination between children who will and will not develop eczema at 3-months of age was high (AUC: 0.91, 95% CI: 0.84–0.98). Conclusions and Clinical Relevance This study demonstrated, for the first time, that FLG expression in UCB is associated with eczema development in infancy. Moreover, our analysis provided prediction models that were capable of discriminating, to a great extent, between those who will and will not develop eczema in infancy. Therefore, early identification of infants at increased risk of developing eczema is possible and such high-risk newborns may benefit from early stratification and intervention.

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Section: Discussionsupporting

confidence: 60%

Expression of the filaggrin gene in umbilical cord blood predicts eczema risk in infancy: A birth cohort study

Ziyab

Ewart

Lockett

et al. 2017

Clin Experimental Allergy

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“…Filaggrin is a key protein for the SC structure, binding keratin filaments in the cytoskeleton and ensuring the flattened annucleated shape of the corneocytes and structure of the cornified envelope [29]. FLG mutations, found in up to 50 % of patients with moderate/severe AD, are associated with disorganized keratin filaments [30].…”

Section: Skin Barrier Function and Impairment In Atopic Dermatitismentioning

confidence: 99%

Skin Barrier Dysfunction and the Atopic March

Clausen

Agner

Thomsen

2015

Curr Treat Options Allergy

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The atopic diseases: atopic dermatitis, asthma and allergic rhinoconjunctivitis are frequent diseases in the population occurring sequentially in the young (the atopic march). The discovery of filaggrin gene (FLG) mutations and impairments in the skin barrier as predisposing factors for atopic dermatitis and subsequent asthma and atopic sensitization in the context of eczema has improved our understanding of the atopic march. The atopic diseases can now be viewed upon as causally related conditions-rather than sequentially occurring manifestations of the same underlying atopic disease state-with atopic dermatitis and FLG mutations being a prerequisite for the development of the other atopic diseases, particularly asthma. This review discusses the role of the skin barrier function, particularly the role of FLG mutations, in the atopic march.

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“…To date, besides the two most common mutations in the European population (R501X and 2282del4), more than 60 mutations have been reported, all leading to loss‐of‐filaggrin expression . There are unique spectrums of filaggrin mutation in different ancestral population, and distinct FLG mutation landscapes have been reported in Asia and Europe; furthermore, prevalence of specific mutations of European (R501X,2282del4) in Asian population is low . The mutation spectrum varies in Asian populations, and few filaggrin mutations are overlapping among some Asian populations.…”

Section: Introductionmentioning

confidence: 99%

“…Filaggrin is a key structural protein that facilitates terminal differentiation of the epidermis and the formation of the stratum corneum (SC), the outermost layer of the skin. 1 Stratum corneum is essential for minimizing water loss through the epidermis and preventing the entry of pathogens, allergens, and toxic chemicals. 2,3 Filaggrin is an abundant histidine-rich protein that plays an important role as nickel chelator in SC.…”

Section: Introductionmentioning

confidence: 99%

Filaggrin gene polymorphisms in Iranian ichthyosis vulgaris and atopic dermatitis patients

et al. 2018

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Background Filaggrin is a key structural epidermal protein in terminal differentiation and formation of skin barrier. The important role of filaggrin and its effects in various cutaneous and noncutaneous disorders initiated a cascade of considerable research in recent years. Loss‐of‐function mutations in FLG, the human gene encoding profilaggrin/filaggrin, is the cause of the common skin condition ichthyosis vulgaris (IV) and major genetic predisposing factor for atopic dermatitis (AD). Several null mutations in the FLG gene that lead to a decrease or absence of filaggrin in skin and predispose these conditions have been described. Objective The aim of this study was to investigative genetic polymorphism of FLG in Iranian patients with IV and AD. Methods In the current study, we carried out full sequencing of the entire FLG coding region in 30 IV patients and 30 AD patients, and also 60 healthy controls. Results In our research, we identified 43 variants reported previously and two novel variants. Conclusion In our study, in the AD and IV patients, loss‐of‐function FLG mutation was not found. This means that another mechanism other than FLG nonsense mutation is involved in the pathogenesis of these patients.

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The Role of Filaggrin in the Skin Barrier and Disease Development

Cited by 30 publications

References 99 publications

Expression of the filaggrin gene in umbilical cord blood predicts eczema risk in infancy: A birth cohort study

Expression of the filaggrin gene in umbilical cord blood predicts eczema risk in infancy: A birth cohort study

Skin Barrier Dysfunction and the Atopic March

Filaggrin gene polymorphisms in Iranian ichthyosis vulgaris and atopic dermatitis patients

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