The prevalence of mutations in the gene encoding filaggrin in the population of Polish patients with atopic dermatitis

Woźniak, Magdalena; Kaczmarek-Skamira, Elżbieta; Romańska-Gocka, Krystyna; Czajkowski, Rafał; Kałużna, Lucyna; Zegarska, Barbara

doi:10.5114/ada.2016.59156

Cited by 8 publications

(9 citation statements)

References 16 publications

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“…In the European population, the prevalence of FLG gene alterations, especially of R501X and 2282del4 mutations, varies among different regions, depending on the ethnic groups [ 3 , 4 , 5 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Filaggrin Loss-of-Function Mutations Are Risk Factors for Severe Food Allergy in Children with Atopic Dermatitis

Astolfi

Cipriani

Messelodi

et al. 2021

JCM

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Atopic dermatitis is frequently associated with the onset of other allergic conditions, such as asthma, rhino-conjunctivitis and food allergy. The etiology of atopic dermatitis is marginally understood in spite of the number of predisposing factors, above all, mutations in the Filaggrin gene (FLG). In this study, the association between loss-of-function variants in the FLG gene and other allergic manifestations, in particular food allergy, was evaluated in an Italian pediatric population affected by atopic dermatitis. The 10 more frequently mutated loci in the FLG gene were genotyped in 238 children affected by atopic dermatitis and tested for association with clinical features of allergic disorders by a multivariate logistic regression model. R501X and 2282del4 were the only two mutations identified; 12.2% of children carry one of these variants, corresponding to an allelic frequency of 6.5%. According to multivariate statistical analysis, loss-of-function variants in the FLG gene represent a risk factor for the onset of severe manifestations of food allergy (OR = 8.9; CI: 3.1–28.3). Peanut and hazelnut were identified as high-risk foods in patients with FLG mutations. This study demonstrates that atopic children carrying FLG mutations represent a high-risk population due to their predisposition to develop severe food allergy reactions, such as anaphylaxis.

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Section: Discussionmentioning

confidence: 99%

Filaggrin Loss-of-Function Mutations Are Risk Factors for Severe Food Allergy in Children with Atopic Dermatitis

Astolfi

Cipriani

Messelodi

et al. 2021

JCM

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“…There were 2 Polish studies that investigated the association between FLG mutations and AD. 33,34 De z bi nska et al 33 found FLG mutations in 2.8% of healthy subjects and 13.8% in AD patients with mild and moderate AD. Wo zniak et al 34 2282del mutations in 30% of AD patients, while no mutations have been discovered in controls.…”

Section: Discussionmentioning

confidence: 99%

“…There are only limited data about the prevalence of FLG mutations in the countries of East and Southern Europe. There were 2 Polish studies that investigated the association between FLG mutations and AD . Dębińska et al .…”

Section: Discussionmentioning

confidence: 99%

Filaggrin loss‐of‐function mutations and levels of filaggrin degradation products in adult patients with atopic dermatitis in Croatia

Tončić

Kežić

Jakaša

et al. 2020

Acad Dermatol Venereol

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Background FLG loss-of-function mutations (FLG LOF) represent the strongest genetic risk factor for atopic dermatitis (AD) and are associated with early-onset and more severe disease. The prevalence of FLG mutations varies greatly across Europe. At present, there are no data on FLG mutation prevalence in Croatian AD patients. Objectives To investigate the prevalence of FLG LOF mutations in adult patients with AD and healthy controls. Next to measure the stratum corneum (SC) levels of filaggrin degradation products (NMF), transepidermal water loss (TEWL) and pH in lesional and non-lesional skin. Methods We recruited 100 AD patients with moderate to severe disease and 50 healthy controls. They were screened for three FLG mutations (R501X, 2282del4 and R2447X). Samples of the SC for NMF analysis were collected by adhesive tapes. TEWL and skin surface pH levels were determined on the lesional and non-lesional skin. Results The combined mutation frequency was 4% in the AD group, and all patients with FLG mutations were homozygous carriers. In the control group, no mutations were found. The most common FLG mutation in AD patients was 2282del4 (3%), followed by R501X (1%). As compared to healthy controls, NMF values were strongly reduced in lesional skin; however, no significant difference was found for non-lesional skin. AD patients had elevated TEWL in both lesional and non-lesional skin. The same pattern was observed for pH. Conclusions Our study expands understanding of the landscape of FLG mutations in the European population. The low frequency of FLG mutations and similar levels of filaggrin degradation products in healthy controls and in non-lesional skin of AD patients suggest that filaggrin deficiency does not confer a major risk for AD in the Croatian population.

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“…Predisposing genetic factors for the development of AD include mutations in genes affecting the integrity of the skin barrier, such as mattrin ( TMEM79 ) and filaggrin (filament aggregation protein, FLG ) . Filaggrin mutations were found in 30% of AD patients in Poland, China (26.0%), and Korea (15.7%), while healthy individuals had none. Importantly, filaggrin expression is downregulated in AD patients independent of their FLG genotype as a consequence of increased type 2 cytokines contributing to the aggravation of disease …”

Section: Introductionmentioning

confidence: 99%

Spontaneous atopic dermatitis in mice with a defective skin barrier is independent of ILC2 and mediated by IL‐1β

Schwartz

Moran

Saunders

et al. 2019

Allergy

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BackgroundAtopic dermatitis (AD) is one of the most common skin diseases with a multifactorial etiology. Mutations leading to loss of skin barrier function are associated with the development of AD with group 2 innate lymphoid cells (ILC2) promoting acute skin inflammation. Filaggrin‐mutant (Flgft/ft) mice develop spontaneous skin inflammation accompanied by an increase in skin ILC2 numbers, IL‐1β production, and other cytokines recapitulating human AD. Here, we investigated the role of ILC2, effector cytokines, inflammasome activation, and mast cell function on the development of chronic AD‐like inflammation in mice.MethodsMice with a frameshift mutation in the filaggrin gene develop spontaneous dermatitis. Flgft/ft mice were crossed to cell‐ or cytokine‐deficient mouse strains, or bred under germ‐free conditions. Skin inflammation was scored, and microbiome composition was analyzed. Skin protein expression was measured by multiplex immunoassay. Infiltrating cells were analyzed by flow cytometry.ResultsWild‐type and Flgft/ft mice significantly differ in their microbiome composition. Furthermore, mutant mice do not develop skin inflammation under germ‐free conditions. ILC2 deficiency did not ameliorate chronic dermatitis in Flgft/ft mice, which was also independent of IL‐4, IL‐5, IL‐9, IL‐13, IL‐17A, and IL‐22. Inflammation was independent of NLRP3 inflammasome activation but required IL‐1β and IL‐1R1‐signaling. Mechanistically, IL‐1β promoted hyperactivation of IL‐1R1‐expressing mast cells. Treatment with anti‐IL‐1β‐antibody alleviated dermatitis exacerbation, while antibiotic intervention ameliorated dermatitis in neonatal mice but not in adults with established inflammation.ConclusionsIn summary, we identified a critical role for the microbiome and IL‐1β mediating chronic inflammation in mice with an impaired skin barrier.

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The prevalence of mutations in the gene encoding filaggrin in the population of Polish patients with atopic dermatitis

Cited by 8 publications

References 16 publications

Filaggrin Loss-of-Function Mutations Are Risk Factors for Severe Food Allergy in Children with Atopic Dermatitis

Filaggrin Loss-of-Function Mutations Are Risk Factors for Severe Food Allergy in Children with Atopic Dermatitis

Filaggrin loss‐of‐function mutations and levels of filaggrin degradation products in adult patients with atopic dermatitis in Croatia

Spontaneous atopic dermatitis in mice with a defective skin barrier is independent of ILC2 and mediated by IL‐1β

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