Dataset Information

Differences in Genetic Variations Between Treatable and Recalcitrant Atopic Dermatitis in Korean.

ABSTRACT: PURPOSE:Variations in barrier- or immune response-related genes are closely related to the development of atopic dermatitis (AD). This study was designed to identify genetic variations and clinical features to predict 'recalcitrant AD.' METHODS:AD patients were classified as treatable and recalcitrant. Treatable AD patients showed satisfactory clinical improvement with basic and topical treatments. Recalcitrant AD patients used systemic immune-suppressants for over 4 weeks as they had not shown clinical improvement with basic and topical treatments. The frequency of gene variations in barrier- (FLG 3321delA, FLG K4022X, KLK7, SPINK 1156, SPINK 1188, SPINK 2475) and immune response- (DEFB1, KDR, IL-5RA, IL-9, and IL-12RB1a, b) related genes were compared between each AD group and the controls. RESULTS:Of all, 249 treatable AD and 32 recalcitrant AD were identified. Heterozygous mutations (Hetero) in KLK7 was more frequent in recalcitrant AD patients than treatable AD, without statistical significance. Hetero in DEFB1 was more frequent in treatable AD patients. However, no other significant genetic differences between treatable and recalcitrant AD was observed. Instead, higher initial Eczema Area Severity Index (EASI) score, serum immunoglobulin E (IgE) level, allergen specific IgE for house dust mites, and family history of atopic diseases were associated with recalcitrant AD with statistical significance. CONCLUSIONS:According to our study, no genetic variation to predict recalcitrant AD was identified, suggesting that clinical manifestation, rather than genetic variations of AD patients is more likely to be an important factor in predicting the prognosis of AD. Further large-scale studies on the correlation between genetic variation and recalcitrant AD are needed.

SUBMITTER: Jun M

PROVIDER: S-EPMC5911443 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Differences in Genetic Variations Between Treatable and Recalcitrant Atopic Dermatitis in Korean.

Jun Myungsoo M Wang Hye Young HY Lee Solam S Choi Eunhee E Lee Hyeyoung H Choi Eung Ho EH

Allergy, asthma & immunology research 20180501 3

<h4>Purpose</h4>Variations in barrier- or immune response-related genes are closely related to the development of atopic dermatitis (AD). This study was designed to identify genetic variations and clinical features to predict 'recalcitrant AD.'<h4>Methods</h4>AD patients were classified as treatable and recalcitrant. Treatable AD patients showed satisfactory clinical improvement with basic and topical treatments. Recalcitrant AD patients used systemic immune-suppressants for over 4 weeks as they ...[more]

PMID: 29676071

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Project description:Several studies have reported negative relations between allergic diseases and school performance but have not simultaneously considered various allergic diseases, including allergic rhinitis, asthma, and atopic dermatitis, and only examined a limited number of participants. The present study investigated the associations of allergic rhinitis, asthma, and atopic dermatitis with school performance in a large, representative Korean adolescent population. A total of 299,695 7th through 12th grade students participated in the Korea Youth Risk Behaviour Web-based Survey (KYRBWS) from 2009 to 2013. The subjects' history of allergic rhinitis, asthma, and atopic dermatitis and number of school absences due to these diseases in the previous 12 months were examined and compared. School performance was classified into 5 levels. The relations between allergic disorders and school performance were analyzed using multiple logistic regressions with complex sampling and adjusted for the subjects' durations of sleep, days of physical activity, body mass indexes (BMIs), regions of residence, economic levels, parents' education levels, stress levels, smoking status, and alcohol use. A subgroup analysis of the economic groups was performed. Allergic rhinitis was positively correlated with better school performance in a dose-dependent manner (adjusted odds ratios, AOR, [95% confidence interval, CI] = 1.50 [1.43-1.56 > 1.33 [1.28-1.38] > 1.17 [1.13-1.22] > 1.09 [1.05-1.14] for grades A > B > C > D; P < 0.001). Asthma was negatively correlated with better school performance (AOR [95% CI] = 0.74 [0.66-0.83], 0.87 [0.79-0.96], 0.83 [0.75-0.91], 0.93 [0.85-1.02] for performance A, B, C, and D, respectively; P < 0.001). Atopic dermatitis was not significantly correlated with school performance. The subgroup analysis of the students' economic levels revealed associations between allergic diseases and school performance. Compared to other allergic disorders, the asthma group had more school absences due to their symptoms (P < 0.001). School performance was positively correlated with allergic rhinitis and negatively correlated with asthma in Korean adolescents, even after adjusting for other variables. The asthma group had an increased number of school absence days, which presumably contributes to these students' poor school performance.

Project description:BACKGROUND:Atopic dermatitis (AD) is a chronic inflammatory disease caused by the complex interaction of genetic, immune and environmental factors. There have many recent discoveries involving the genetic and epigenetic studies of AD. METHODS:A retrospective PubMed search was carried out from June 2009 to June 2016 using the terms "atopic dermatitis", "association", "eczema", "gene", "polymorphism", "mutation", "variant", "genome wide association study", "microarray" "gene profiling", "RNA sequencing", "epigenetics" and "microRNA". A total of 132 publications in English were identified. RESULTS:To elucidate the genetic factors for AD pathogenesis, candidate gene association studies, genome-wide association studies (GWAS) and transcriptomic profiling assays have been performed in this period. Epigenetic mechanisms for AD development, including genomic DNA modification and microRNA posttranscriptional regulation, have been explored. To date, candidate gene association studies indicate that filaggrin (FLG) null gene mutations are the most significant known risk factor for AD, and genes in the type 2 T helper lymphocyte (Th2) signaling pathways are the second replicated genetic risk factor for AD. GWAS studies identified 34 risk loci for AD, these loci also suggest that genes in immune responses and epidermal skin barrier functions are associated with AD. Additionally, gene profiling assays demonstrated AD is associated with decreased gene expression of epidermal differentiation complex genes and elevated Th2 and Th17 genes. Hypomethylation of TSLP and FCER1G in AD were reported; and miR-155, which target the immune suppressor CTLA-4, was found to be significantly over-expressed in infiltrating T cells in AD skin lesions. CONCLUSIONS:The results suggest that two major biologic pathways are responsible for AD etiology: skin epithelial function and innate/adaptive immune responses. The dysfunctional epidermal barrier and immune responses reciprocally affect each other, and thereby drive development of AD.

Project description:BackgroundAutism, a childhood behavioral disorder, belongs to a large suite of diseases, collectively referred to as autism spectrum disorders (ASD). Though multifactorial in etiology, approximately 10% of ASD are associated with atopic dermatitis (AD). Moreover, ASD prevalence increases further as AD severity worsens, though these disorders share no common causative mutations. We assessed here the link between these two disorders in the standard, valproic acid mouse model of ASD. In prior studies, there was no evidence of skin involvement, but we hypothesized that cutaneous involvement could be detected in experiments conducted in BALB/c mice. BALB/c is an albino, laboratory-bred strain of the house mouse and is among the most widely used inbred strains used in animal experimentation.MethodsWe performed our studies in valproic acid (VPA)-treated BALB/c hairless mice, a standard mouse model of ASD. Mid-trimester pregnant mice received a single intraperitoneal injection of either valproic acid sodium salt dissolved in saline or saline alone on embryonic day 12.5 and were housed individually until postnatal day 21. Only the brain and epidermis appeared to be affected, while other tissues remain unchanged. At various postnatal time points, brain, skin and blood samples were obtained for histology and for quantitation of tissue sphingolipid content and cytokine levels.ResultsAD-like changes in ceramide content occurred by day one postpartum in both VPA-treated mouse skin and brain. The temporal co-emergence of AD and ASD, and the AD phenotype-dependent increase in ASD prevalence correlated with early appearance of cytokine markers (i.e., interleukin [IL]-4, 5, and 13), as well as mast cells in skin and brain. The high levels of interferon (IFN)γ not only in skin, but also in brain likely account for a significant decline in esterified very-long-chain N-acyl fatty acids in brain ceramides, again mimicking known IFNγ-induced changes in AD.ConclusionBaseline involvement of both AD and ASD could reflect concurrent neuro- and epidermal toxicity, possibly because both epidermis and neural tissues originate from the embryonic neuroectoderm. These studies illuminate the shared susceptibility of the brain and epidermis to a known neurotoxin, suggesting that the atopic diathesis could be extended to include ASD.

Dataset Information

Differences in Genetic Variations Between Treatable and Recalcitrant Atopic Dermatitis in Korean.

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Differences in Genetic Variations Between Treatable and Recalcitrant Atopic Dermatitis in Korean.

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