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1.
Int Arch Allergy Immunol ; 180(4): 235-243, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31694044

RESUMO

Over the last decades, an increasing appearance of allergies and atopic disorders, such as asthma, dermatitis, and rhinitis, has been observed. The mechanisms of these disorders remain unclear, and therefore the development of novel therapies is limited. Current treatments are often symptomatic, nonspecific, or may have severe side effects. Further insights into the mechanisms of the underlying disease pathogenesis could reveal novel targets for treatment. In this review, we provide an update on recent basic and translational studies that offer novel insights and opportunities for the treatment of patients with atopic disorders.


Assuntos
Asma/etiologia , Dermatite Atópica/etiologia , Hipersensibilidade Alimentar/etiologia , Rinite Alérgica/etiologia , Alérgenos/imunologia , Asma/genética , Asma/terapia , Dermatite Atópica/genética , Dermatite Atópica/terapia , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/terapia , Predisposição Genética para Doença/genética , Humanos , Rinite Alérgica/genética , Rinite Alérgica/terapia , Fatores de Risco
2.
Nat Commun ; 10(1): 4703, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619666

RESUMO

Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis.


Assuntos
Dermatite Atópica/genética , Interações entre Hospedeiro e Microrganismos/genética , Microbiota/genética , Psoríase/genética , Pele/metabolismo , Pele/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Dermatite Atópica/microbiologia , Disbiose/genética , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/microbiologia , RNA Ribossômico 16S , Adulto Jovem
3.
Vet Dermatol ; 30(5): 396-e119, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31407839

RESUMO

BACKGROUND: Canine atopic dermatitis (cAD) is one the most common and distressing skin disorders seen in dogs. It is characterized by dysfunction in the skin barrier, with a complex pathogenesis combining both genetic and environmental factors. OBJECTIVES: To evaluate associations between environmental factors and case-control status in two closely related, at-risk breeds, the Labrador retriever and golden retriever. ANIMALS: Two thousand four hundred and forty-five pet dogs, of which 793 were classed as cases (575 Labrador and 218 golden retrievers) and 1,652 as controls (1,120 Labrador and 532 golden retrievers). METHODS AND MATERIALS: Case-control status was assigned based upon owner response to a standardized validated questionnaire. Retrospective data on rearing environment were collected via additional questions. Univariate and multivariate logistic regressions were utilized to evaluate associations between environmental factors and case-control status. RESULTS: Risk factors included being reared in an urban environment (not living currently in an urban environment), being male, being neutered, receiving flea control and being allowed on upholstered furniture. Protective factors included living with other dogs (not cats) and walking in woodlands, fields or beaches. Additionally, amongst Labrador retrievers, chocolate-coloured dogs were at greater risk of having cAD than black- or yellow-coated dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: This study is the largest of its kind to date to investigate the role of the environment in cAD. Although precise triggers are unclear, this study complements earlier studies in highlighting the protective role of a rural environment and some novel associations with disease development.


Assuntos
Dermatite Atópica/veterinária , Doenças do Cão/etiologia , Meio Ambiente , Animais , Dermatite Atópica/etiologia , Dermatite Atópica/genética , Doenças do Cão/genética , Cães , Feminino , Predisposição Genética para Doença , Masculino , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Fatores de Risco
4.
BMC Med Genomics ; 12(1): 121, 2019 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-31420038

RESUMO

BACKGROUND: Psoriasis and atopic dermatitis are two inflammatory skin diseases with a high prevalence and a significant burden on the patients. Underlying molecular mechanisms include chronic inflammation and abnormal proliferation. However, the cell types contributing to these molecular mechanisms are much less understood. Recently, deconvolution methodologies have allowed the digital quantification of cell types in bulk tissue based on mRNA expression data from biopsies. Using these methods to study the cellular composition of the skin enables the rapid enumeration of multiple cell types, providing insight into the numerical changes of cell types associated with chronic inflammatory skin conditions. Here, we use deconvolution to enumerate the cellular composition of the skin and estimate changes related to onset, progress, and treatment of these skin diseases. METHODS: A novel signature matrix, i.e. DerM22, containing expression data from 22 reference cell types, is used, in combination with the CIBERSORT algorithm, to identify and quantify the cellular subsets within whole skin biopsy samples. We apply the approach to public microarray mRNA expression data from the skin layers and 648 samples from healthy subjects and patients with psoriasis or atopic dermatitis. The methodology is validated by comparison to experimental results from flow cytometry and immunohistochemistry studies, and the deconvolution of independent data from isolated cell types. RESULTS: We derived the relative abundance of cell types from healthy, lesional, and non-lesional skin and observed a marked increase in the abundance of keratinocytes and leukocytes in the lesions of both inflammatory dermatological conditions. The relative fraction of these cells varied from healthy to diseased skin and from non-lesional to lesional skin. We show that changes in the relative abundance of skin-related cell types can be used to distinguish between mild and severe cases of psoriasis and atopic dermatitis, and trace the effect of treatment. CONCLUSIONS: Our analysis demonstrates the value of this new resource in interpreting skin-derived transcriptomics data by enabling the direct quantification of cell types in a skin sample and the characterization of pathological changes in tissue composition.


Assuntos
Inflamação/patologia , Pele/patologia , Biópsia , Doença Crônica , Bases de Dados Genéticas , Dermatite Atópica/genética , Regulação da Expressão Gênica , Humanos , Inflamação/genética , Queratinócitos/patologia , Psoríase/genética , Reprodutibilidade dos Testes
5.
J Autism Dev Disord ; 49(11): 4626-4633, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31435817

RESUMO

Several studies have shown a strong association between atopic diseases and autism spectrum disorder (ASD). However, the risk of atopic diseases in individuals having ASD-affected siblings has never been investigated. This nationwide population-based cohort study included 2762 individuals with ASD-affected siblings and 11,048 controls. Diagnoses of atopic diseases, including asthma, atopic dermatitis, allergic rhinitis, and allergic conjunctivitis, were ascertained from 1996 or the birth data to the end of 2011. Individuals with ASD-affected siblings had a higher risk for asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, and multiple atopic diseases compared with controls. In conclusion, individuals with ASD-affected siblings were more likely than were the controls to develop atopic diseases, suggesting shared familial mechanisms underlying the two conditions.


Assuntos
Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/genética , Dermatite Atópica/epidemiologia , Dermatite Atópica/genética , Vigilância da População , Irmãos , Adolescente , Asma/epidemiologia , Asma/genética , Asma/psicologia , Transtorno do Espectro Autista/psicologia , Criança , Estudos de Coortes , Dermatite Atópica/psicologia , Feminino , Humanos , Masculino , Fatores de Risco , Irmãos/psicologia , Taiwan/epidemiologia
6.
Biomed Res Int ; 2019: 3457898, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275967

RESUMO

To date, the genes associated with susceptibility to Atopic Eczema (AE) are mainly implicated in immunity, inflammation, and maintenance of skin barrier. Little is known about the possible relationship between genes modulating Extra-Cellular Matrix (ECM) and AE etiopathogenesis. In this regard, the primary objective of the present study has been the investigation of susceptibility biomarkers localized within genes encoding collagen proteins. Several studies have shown that polymorphisms within the genes encoding such proteins may generate abnormal connective tissues, making them more susceptible to mechanical stress, loss of epidermal integrity, and aging. We therefore decided to investigate three polymorphisms located in COL6A5, COL8A1, and COL10A1 as potential susceptibility biomarkers for AE in a cohort of 1470 subjects of Mediterranean origin. The genes of interest have been selected considering that the ECM and immune/inflammatory response are strongly dysregulated in AE and other complex disorders. The study confirmed that the susceptibility to AE depends on a complex interaction between latitude, geographical localization, and the differential distribution of genetic variants among populations exposed to similar environmental factors.


Assuntos
Colágeno Tipo VIII/genética , Colágeno Tipo VI/genética , Colágeno Tipo X/genética , Dermatite Atópica/genética , Predisposição Genética para Doença , Estudos de Casos e Controles , Humanos , Região do Mediterrâneo , Polimorfismo de Nucleotídeo Único/genética
7.
Med Sci Monit ; 25: 4353-4361, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31184315

RESUMO

BACKGROUND Atopic dermatitis is a chronic inflammatory disease of the skin. It has a high prevalence worldwide and affected persons are prone to recurrent attacks, seriously affecting the physical and mental of patients. The exact etiology of the disease is still unclear. MATERIAL AND METHODS There are 7 datasets on atopic dermatitis in the Gene Expression Omnibus database, including 142 lesional and 134 non-lesional skin biopsy samples. Differential analysis was performed after datasets were integrated by robust multi-array average method. Functional modules of GSE99802 were explored by weighted gene co-expression network analysis. The 4 most important modules were enriched into the pathways by Metascape. RESULTS Significantly differentially expressed genes included 41 upregulated and 10 downregulated genes. The following 5 of the most important upregulated genes had the strongest association with atopic dermatitis. SERPINB3&4 promote inflammation and impaired skin barrier function in the early stage of atopic dermatitis. S100A9 aggravates the inflammatory response by inducing the activation of toll-like receptor 4, neutrophil chemotaxis, neutrophilic inflammation, and the amplification of interleukin-8. MMP1 is the key protease of skin collagen degradation, keeping the extracellular matrix in dynamic balance. MMP12 induces the aggregation of various inflammatory cells into inflammatory tissue. The enriched pathways of each module mainly include Cellular responses to external stimuli, Metabolism of RNA and Translation, and Infectious disease. CONCLUSIONS The associated pathways and genes not only help us understand the molecular mechanism of the disease, but also provide research directions or targets for accurate diagnosis and treatment.


Assuntos
Dermatite Atópica/genética , Dermatite Atópica/patologia , Expressão Gênica/genética , Análise por Conglomerados , Biologia Computacional/métodos , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos , Estudos de Associação Genética/métodos , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Pele/patologia
8.
Dermatology ; 235(5): 355-364, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31203284

RESUMO

Atopic dermatitis (AD) is a complex disease that is thought to be triggered by environmental factors in genetically susceptible individuals. Twin studies have estimated the heritability of AD to be approximately 75%, with the null (loss-of-function) mutations of the gene encoding filaggrin (FLG) (chromosome 1q21.3) as the strongest known genetic risk factor. The discovery of the filaggrin gene was important in the emerging model for AD pathogenesis, combining skin barrier function with adaptive and innate immunity. Assisted by the recent development of large-scale high-throughput genomics, more than 30 genetic loci have been linked to AD across different populations. Identification of these loci, together with functional studies, has already provided new insights into disease biology and identified novel drug targets. Further, these susceptibility loci are laying the groundwork for phenome-wide association studies to test their multiple phenotype relationships and application of Mendelian randomization to investigate causal relationships. Despite many known genes, a majority of the genetic risk for AD is yet unexplored. Therefore, studies investigating refined phenotype groups, low-frequency and rare genetic variation, gene-gene and/or gene-environment interactions, epigenetic mechanisms and data from multi-omics technologies are warranted. In this review, we describe genetic discoveries for AD, including results from candidate gene studies, studies of AD-like genetic diseases, genome-wide association studies and genetic sequencing studies. We explain how some of these genetic discoveries have unraveled new mechanistic insights into the pathogenesis of AD and exemplify how personal genetic data could be used for preventive strategies and a tailored treatment regimen (i.e., precision medicine).


Assuntos
Dermatite Atópica/genética , Dermatite Atópica/imunologia , Proteínas S100/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Mutação
9.
Immunol Med ; 42(1): 10-15, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31204894

RESUMO

Atopic dermatitis (AD) is caused by complex interactions between a variety of genetic and environmental factors that contribute to the maintenance of the chronic inflammatory skin condition. Most conventional treatments have been designed for the so-called 'average patient'. In recent years however, many previously unknown details pertaining to the mechanisms of the pathogenesis of AD have been elucidated, and novel treatments based on these pathological mechanisms or on subgroup classifications have been developed. Herein, how future treatment strategies for AD can be developed is described.


Assuntos
Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/etiologia , Terapia de Alvo Molecular/tendências , Animais , Anticorpos , Anticorpos Monoclonais/uso terapêutico , Dermatite Atópica/genética , Dermatite Atópica/imunologia , Humanos , Imunoglobulina E/imunologia , Subunidade alfa de Receptor de Interleucina-4/imunologia , Proteínas de Filamentos Intermediários/genética , Camundongos , Mutação , Ácidos Nucleicos/uso terapêutico , Oligodesoxirribonucleotídeos/uso terapêutico , Fator de Transcrição STAT6 , beta-Defensinas
10.
Biochem Med (Zagreb) ; 29(2): 020501, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31223255

RESUMO

There is an increasing number of experimental, genetic and clinical evidence of atopic dermatitis expression as a pre-condition for later development of other atopic diseases such as asthma, food allergy and allergic rhinitis. Atopic dermatitis is a heterogeneous, recurrent childhood disease, also present in the adult age. It is increasingly attributed to systemic features and is characterized by immunological and skin barrier integrity and function dysregulation. To maintain the protective function of the skin barrier, in particular the maintenance of pH, hydration and antimicrobial functions, the filaggrin, among others, plays a significant role. Filaggrin is a multifunctional, histidine-rich, insoluble protein. The lack of filaggrin is associated with various cutaneous (e.g. ichthyosis vulgaris, allergic contact dermatitis) and non-cutaneous (e.g. diabetes, inflammatory conditions of the gastrointestinal tract) diseases and may be a result of genetic, immunological factors combined with environmental factors. In this review we summarised (emphasized) recent findings in understanding the role of filaggrin in atopic dermatitis and other diseases, participants in the atopic march.


Assuntos
Dermatite Atópica , Proteínas de Filamentos Intermediários , Dermatite Atópica/diagnóstico , Dermatite Atópica/genética , Dermatite Atópica/metabolismo , Humanos , Proteínas de Filamentos Intermediários/análise , Proteínas de Filamentos Intermediários/genética , Proteínas de Filamentos Intermediários/metabolismo
11.
J Hum Genet ; 64(9): 911-917, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31249362

RESUMO

Atopic dermatitis (AD) is a chronic inflammatory skin disease, and skin barrier defects are often observed in patients with AD. So far, few association studies between FLG loss-of-function mutations and onset of AD in longitudinal studies of early childhood have been reported. In the present study, we aimed to investigate the effect of FLG loss-of-function mutations on the development of AD in a longitudinal birth cohort study. The status of AD diagnosis at each age until 6 years was collected from the Tokyo Children's Health, Illness, and Development (T-CHILD) study. We analyzed eight loss-of-function mutations in FLG in 712 participants. FLG loss-of-function mutations were significantly associated with AD onset in infancy (≤2 years) (P < 0.001, OR 3.54, 95% CI 1.88-6.65), but not with AD onset in childhood (≥3 years) (P = 0.981, OR 0.99, 95% CI 0.29-3.36), and none of the children in the present cohort who developed AD at 5 years of age or later carried FLG loss-of-function mutations. Our data support the notion that the effect of FLG loss-of-function mutations is prominent during a very early stage of life.


Assuntos
Dermatite Atópica , Mutação com Perda de Função , Proteínas S100/genética , Criança , Pré-Escolar , Dermatite Atópica/genética , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Feminino , Seguimentos , Humanos , Lactente , Estudos Longitudinais , Masculino , Proteínas S100/metabolismo
12.
Semin Cutan Med Surg ; 38(1): E12-E18, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31051018

RESUMO

Skinomics is a field of bioinformatics applied specifically to skin biology and, by extension, to dermatology. Skinomics has been expanding into extensive genome-wide association studies, eg, of psoriasis, proteomics, lipidomics, metabolomics, metagenomics, and the studies of the microbiome. Here, the current state of the field of transcriptomics is reviewed, including the studies of the gene expression in human skin under several healthy and disease conditions. Specifically, transcriptional studies of epidermal differentiation, skin aging, effects of cytokines, inflammation with emphases on psoriasis and atopic dermatitis, and wound healing are reviewed. The transition from microarrays to NextGen sequencing is noted and potential future directions suggested.


Assuntos
Epiderme/metabolismo , Biologia Computacional , Dermatite Atópica/genética , Perfilação da Expressão Gênica , Humanos , Psoríase/genética , Envelhecimento da Pele/genética , Transcriptoma
14.
BMC Med Genet ; 20(1): 83, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101031

RESUMO

BACKGROUND: We retrieved different reports containing different genetic effects of - 1082 A/G, - 819 T/C, and - 592 A/C polymorphisms within the IL-10 (interleukin-10) gene on the susceptibility to clinical atopic dermatitis. METHODS: Herein, we conducted a meta-analysis to comprehensively assess such a genetic relationship after collecting the available published evidence. STATA 12.0 software was used for the statistical analysis under the allelic, homozygotic, heterozygotic, dominant, recessive and carrier genetic models. RESULTS: By retrieving and screening database literature, a total of 16 eligible case-control studies were finally selected. For the IL-10 -1082 A/G polymorphism, we did not detect a significant difference between atopic dermatitis cases and population-based controls in the overall meta-analysis under the genetic models of allele G vs. A (P = 0.540), GG vs. AA (P = 0.853), AG vs AA (P = 0.265), AG + GG vs AA (P = 0.221), GG vs AA+AG (P = 0.540) and carrier G vs. A (P = 0.643). Moreover, a statistically non-significant association was observed in the most subgroup meta-analyses by the factors of ethnicity, country and Hardy-Weinberg equilibrium. Likewise, the negative results were detected for the synthetic analysis of IL-10 -819 T/C and - 592 C/A polymorphisms. CONCLUSION: The current evidence does not support a strong genetic relationship between IL-10 -1082 A/G, - 819 T/C and - 592 A/C polymorphisms and the susceptibility to atopic dermatitis.


Assuntos
Dermatite Atópica/genética , Predisposição Genética para Doença , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único , Humanos
15.
APMIS ; 127(5): 386-424, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31124204

RESUMO

The current state, tools, and applications of personalized medicine with special emphasis on inflammatory skin diseases like psoriasis and atopic dermatitis are discussed. Inflammatory pathways are outlined as well as potential targets for monoclonal antibodies and small-molecule inhibitors.


Assuntos
Dermatite Atópica/tratamento farmacológico , Medicina de Precisão , Psoríase/tratamento farmacológico , Câmaras de Exposição Atmosférica , Biomarcadores , Dermatite Atópica/etiologia , Dermatite Atópica/genética , Epigenômica , Humanos , Testes Farmacogenômicos , Medicina de Precisão/métodos , Proteômica , Transcriptoma , Sequenciamento Completo do Genoma
16.
Skin Pharmacol Physiol ; 32(4): 192-200, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31096247

RESUMO

BACKGROUND: Atopic diseases constitute a major health challenge for industrialized countries, and elevated levels of interleukin 4 (IL-4) frequently characterize these disorders. Previous in vitroanalyses have indicated that IL-4 strongly upregulates the expression of IL-4-sensitive genes in human monocytes. OBJECTIVE: To explore whether similar expression alterations may contribute to the pathomechanisms of atopic diseases in vivo we carried out a small-scale case-control clinical study (n = 43), in which we quantified the plasma levels of IgE and IL-4 as well as the expression of selected IL-4-sensitive genes in blood leukocytes. METHODS: 34 allergic patients suffering from allergic rhinitis (n = 11), atopic eczema (n = 11) and allergic asthma (n = 12) as well as 9 healthy control individuals were recruited. IgE and IL-4 plasma levels were determined by ELISA, and the expression of selected IL-4-sensitive gene products in blood leukocytes was quantified by qRT-PCR. In addition, the fatty acid oxygenase activity of isolated monocytes was measured by RP-HPLC analysis of the arachidonic acid oxygenation products (ex vivo activity assays). RESULTS: We found that plasma levels of IgE and IL-4 were significantly elevated in atopic patients but the degree of elevation was not sufficient to upregulate the expression of the selected IL-4-sensitive genes in circulating leukocytes. Moreover, the arachidonic acid oxygenase activity of blood monocytes was not significantly altered in atopic patients. CONCLUSION: Our data suggest that the IL-4 plasma levels of atopic patients are not high enough to impact the expression of IL-4-sensitive genes.


Assuntos
Hipersensibilidade Imediata/sangue , Hipersensibilidade Imediata/genética , Imunoglobulina E/biossíntese , Interleucina-4/biossíntese , Leucócitos/fisiologia , Adulto , Asma/sangue , Asma/genética , Estudos de Casos e Controles , Dermatite Atópica/sangue , Dermatite Atópica/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigenases/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Rinite Alérgica/sangue , Rinite Alérgica/genética , Regulação para Cima
17.
Biofactors ; 45(4): 536-547, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31087730

RESUMO

The effects of environmental insults on human health are a major global concern. Some of the most noxious pollutants that humans are exposed to include ozone (O3 ), particulate matter (PM), and cigarette smoke (CS). Since the skin is the first line of defense against environmental insults, it is considered one of the main target organs for the harmful insults of air pollution. Thus, there is solid evidence that skin pathologies such as premature aging, atopic dermatitis (AD), and psoriasis are associated with pollutant exposure; all of these skin conditions are also associated with an altered redox status. Therefore, although the mechanisms of action and concentrations of O3 , PM, and CS that we are exposed to differ, exposure to all of these pollutants is associated with the development of similar skin conditions due to the fact that all of these pollutants alter redox homeostasis, increasing reactive oxygen species production and oxidative stress. A main product of oxidative stress, induced by exposure to the aforementioned pollutants, is 4-hydroxy-2-nonenal (HNE), which derives from the oxidation of ω-6 polyunsaturated fatty acids. HNE is a highly reactive compound that can form adducts with cellular proteins and even DNA; it is also an efficient cell signaling molecule able to regulate mitogen-activated protein kinase pathways and the activity of redox-sensitive transcription factors such as Nrf2, AP1, and NFκB. Therefore, increased levels of HNE in the skin, in response to pollutants, likely accelerates skin aging and exacerbates existing skin inflammatory conditions; thus, targeting HNE formation could be an innovative cosmeceutical approach for topical applications.


Assuntos
Poluentes Atmosféricos/toxicidade , Aldeídos/toxicidade , Dermatite Atópica/induzido quimicamente , Material Particulado/toxicidade , Psoríase/induzido quimicamente , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Poluentes Atmosféricos/metabolismo , Aldeídos/metabolismo , Dermatite Atópica/genética , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Oxirredução , Estresse Oxidativo , Ozônio/metabolismo , Ozônio/toxicidade , Psoríase/genética , Psoríase/metabolismo , Psoríase/patologia , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Pele/metabolismo , Pele/patologia , Envelhecimento da Pele/genética , Envelhecimento da Pele/patologia , Poluição por Fumaça de Tabaco/efeitos adversos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
Genet Test Mol Biomarkers ; 23(5): 332-341, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30932690

RESUMO

Aims: The aim of this study was to summarize the currently available evidence on the associations between the IL-10-1082G/A, IL-10-592A/C, and IL-10-819G/A polymorphisms and susceptibility to atopic dermatitis (AD). Materials and Methods: Five electronic databases including PubMed, the Web of Science, Excerpta Medica dataBASE, the Cochrane Library, and the China National Knowledge Infrastructure were searched for potential studies. Studies illustrating the association of the IL-10-1082G/A, IL-10-592A/C, and IL-10-819G/A polymorphisms and AD susceptibility were included in this meta-analysis. For a study to be included, it had to have been published before September 20, 2018. Study quality was assessed using the Newcastle-Ottawa scale. Summary odds ratios and 95% confidence intervals were calculated to evaluate potential associations under five genetic models. Results: A total of 15 case-control studies comprising of 1647 AD patients and 2031 controls were included in this meta-analysis. Their methodological qualities were generally high. We confirmed an association between the IL-10-819G/A polymorphism and AD, but there was an insignificant association identified between the IL-10-1082G/A and the IL-10-592A/C polymorphisms and AD when all ethnic groups were considered together. The subgroup analyses revealed some ethnic-specific effects. For the IL-10-819G/A polymorphism, individuals with the GG-genotype seemed to have an increased risk of AD among Caucasian populations, but less so in the Asian populations. However, for the IL-10-1082G/A polymorphism, the GG-genotype carriers seemed to be more susceptible to AD in the Asian populations than in the Caucasian populations. Conclusions: This meta-analysis suggests that the IL-10-819G/A polymorphism seems to be associated with increased risk of AD among Caucasian populations, and that the IL-10-1082G/A polymorphism seems to be correlated with AD among Asian populations.


Assuntos
Dermatite Atópica/genética , Interleucina-10/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Fatores de Risco
19.
Vet Immunol Immunopathol ; 209: 1-6, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30885300

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a common disease of dogs and humans. In both species, the interplay of genetic and environmental factors affect disease expression. In dogs with AD, differences in the breed studied and in their geographical origin have led to heterogeneity in genetic association and while different loci have been identified, a causative genetic mutation has not. We hypothesized that AD could be mapped in a large cohort of rigorously phenotyped, geographically restricted West Highland White Terriers (WHWT), a breed with a high prevalence of the disease. OBJECTIVES: A) Collect phenotypes and DNA from a large cohort of WHWT born in the USA. B) Perform a genome-wide association study (GWAS) for AD in these dogs to identify associated regions and genes of interest. C) Sequence genes of interest to identify pathologic variants. METHODS: We collected DNA from 96 WHWT with AD and 87 controls from the same breed. DNA was isolated and dogs were genotyped using the Illumina CanineHD BeadChip. A GWAS was performed using EMMAX and associated regions were examined for genes of interest. Genes with possible relevance to AD were examined more closely in two affected and two normal WHWT using next-generation sequencing. Variants in these genes that were unique to the two affected WHWT were compared to a database of variants derived from whole genome sequencing of 200 non-WHWT dogs across 33 additional breeds. RESULTS: The GWAS identified a 2.7 Mb genomic region on CFA3 that included 37 genes. There was a missense variant in the F2R gene in both affected dogs but this variant was also found in 35 dogs in 9 breeds in the database of whole genome sequences for whom the phenotype regarding atopic dermatitis was unknown. CONCLUSIONS: Atopic dermatitis in WHWT is associated with a region on CFA3 that contains several candidate genes. Of these, a homozygous variant in the F2R gene present in multiple breeds that also suffer from AD warrants further evaluation.


Assuntos
Dermatite Atópica/veterinária , Doenças do Cão/genética , Animais , Estudos de Coortes , Dermatite Atópica/genética , Cães , Feminino , Estudo de Associação Genômica Ampla/veterinária , Técnicas de Genotipagem/veterinária , Masculino , Polimorfismo de Nucleotídeo Único
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