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Genome-wide association study of recalcitrant atopic dermatitis in Korean children.

ABSTRACT: Atopic dermatitis (AD) is a heterogeneous chronic inflammatory skin disease. Most AD during infancy resolves during childhood, but moderate-to-severe AD with allergic sensitization is more likely to persist into adulthood and more often occurs with other allergic diseases.We sought to find susceptibility loci by performing the first genome-wide association study (GWAS) of AD in Korean children with recalcitrant AD, which was defined as moderate-to-severe AD with allergic sensitization.Our study included 246 children with recalcitrant AD and 551 adult control subjects with a negative history of both allergic disease and allergic sensitization. DNA from these subjects was genotyped; sets of common single nucleotide polymorphisms (SNPs) were imputed and used in the GWAS after quality control checks.SNPs at a region on 13q21.31 were associated with recalcitrant AD at a genome-wide threshold of significance (P < 2.0 × 10(-8)). These associated SNPs are more than 1 Mb from the closest gene, protocadherin (PCDH)9. SNPs at 4 additional loci had P values of less than 1 × 10(-6), including SNPs at or near the neuroblastoma amplified sequence (NBAS; 2p24.3), thymus-expressed molecule involved in selection (THEMIS; 6q22.33), GATA3 (10p14), and S-phase cyclin A-associated protein in the ER (SCAPER; 15q24.3) genes. Further analysis of total serum IgE levels suggested 13q21.31 might be primarily an IgE locus, and analyses of published data demonstrated that SNPs at the 15q24.3 region are expression quantitative trait loci for 2 nearby genes, ISL2 and proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), in immune cells.Our GWAS of recalcitrant AD identified new susceptibility regions containing genes involved in epithelial cell function and immune dysregulation, 2 key features of AD, and potentially extend our understanding of their role in pathogenesis.

SUBMITTER: Kim KW

PROVIDER: S-EPMC4562879 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Genome-wide association study of recalcitrant atopic dermatitis in Korean children.

Kim Kyung Won KW Myers Rachel A RA Lee Ji Hyun JH Igartua Catherine C Lee Kyung Eun KE Kim Yoon Hee YH Kim Eun-Jin EJ Yoon Dankyu D Lee Joo-Shil JS Hirota Tomomitsu T Tamari Mayumi M Takahashi Atsushi A Kubo Michiaki M Choi Je-Min JM Kim Kyu-Earn KE Nicolae Dan L DL Ober Carole C Sohn Myung Hyun MH

The Journal of allergy and clinical immunology 20150430 3

<h4>Background</h4>Atopic dermatitis (AD) is a heterogeneous chronic inflammatory skin disease. Most AD during infancy resolves during childhood, but moderate-to-severe AD with allergic sensitization is more likely to persist into adulthood and more often occurs with other allergic diseases.<h4>Objective</h4>We sought to find susceptibility loci by performing the first genome-wide association study (GWAS) of AD in Korean children with recalcitrant AD, which was defined as moderate-to-severe AD w ...[more]

PMID: 25935106

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Project description:ImportancePruritus, a hallmark of atopic dermatitis (AD), is thought to disrupt sleep, yet little is known about how variations in disease activity and severity of this common childhood condition may be associated with sleep patterns over time.ObjectiveTo determine whether children with active AD have impaired sleep duration and quality at multiple time points throughout childhood and whether disease severity affects sleep outcomes.Design, setting, and participantsThis longitudinal cohort study used data of children enrolled in the Avon Longitudinal Study of Parents and Children, a population-based birth cohort in Avon, United Kingdom. Participants were children (N = 13 988) alive at 1 year and followed up with repeated measures of self-reported AD and sleep through 16 years of age. This study was based on data collected from 1990 to 2008. Data analysis was performed from September 2017 to September 2018.Main outcomes and measuresStandardized measure of sleep duration and composite measure of sleep quality, including nighttime awakenings, early morning awakenings, difficulty falling asleep, and nightmares, were repeated at multiple time points between 2 and 16 years of age.ResultsThe study sample comprised 13 988 children (7220 male [51.6%]) followed up for a median (interquartile range [IQR]) duration of 11 (5-14) years. Of this total, 4938 children (35.3%) met the definition of having atopic dermatitis between 2 and 16 years of age. Total sleep duration was similar between children with active AD and without AD at all ages, and the average estimated difference across childhood was a clinically negligible difference of 2 minutes less per day for children with AD (95% CI, -4 to 0 minutes). In contrast, children with active AD were more likely to report worse sleep quality at all time points, with a nearly 50% higher odds of experiencing more sleep-quality disturbances (adjusted odds ratio [aOR], 1.48; 95% CI, 1.33 to 1.66). Children with more severe active disease (quite bad or very bad AD: aOR, 1.68; 95% CI, 1.42 to 1.98) and with comorbid asthma or allergic rhinitis (aOR, 1.79; 95% CI, 1.54 to 2.09) had worse sleep quality. However, even children with mild AD (OR, 1.40; 95% CI, 1.27 to 1.54) or inactive AD (OR, 1.41; 95% CI, 1.28 to 1.55) had statistically significantly increased odds of impaired sleep quality.Conclusions and relevanceAtopic dermatitis appeared to be associated with impaired sleep quality throughout childhood; thus, it is suggested that clinicians should consider sleep quality among all children with AD, especially those with comorbid asthma or allergic rhinitis and severe disease, and that interventions to improve sleep quality are needed.

Dataset Information

Genome-wide association study of recalcitrant atopic dermatitis in Korean children.

Publications

Genome-wide association study of recalcitrant atopic dermatitis in Korean children.

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