Association between fine mapping thymic stromal lymphopoietin and atopic dermatitis onset and persistence
Association between fine mapping thymic stromal lymphopoietin and atopic dermatitis onset and persistence
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DOI：
10.1016/j.anai.2019.08.018
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发表时间：
2019-12-01
影响因子：
5.9
通讯作者：
Margolis, David J.
中科院分区：
文献类型：
--
作者：
Lou, Carolyn;Mitra, Nandita;Margolis, David J.
Background: Atopic dermatitis (AD) is a common chronic relapsing skin disease. Genetic variants have been associated with skin barrier function and immune regulation. Thymic stromal lymphopoietin (TSLP), an immune regulator, has been previously associated with AD.Objective: To fine map TSLP and evaluate associations with the onset and persistence of AD.Methods: TSLP variation was determined using targeted massively parallel sequencing in a longitudinal cohort of children with AD. Evaluations included linkage disequilibrium and the persistence of AD for as many as 10 years of follow-up. The association between the presence of AD and rs1898671 variation was evaluated in a second independent cohort.Results: The minor variant frequency for rs1898671 was 23.5% (95% CI, 21.4%-25.8%). This variant was not in linkage disequilibrium with other TSLP variants in the longitudinal cohort (n = 741). White children with AD were less likely to have rs1898671 variant (odds ratio [OR], 1.41; 95% CI, 1.20-1.66) than Genome Aggregation Database controls. Children with AD and the rs1898671 variant during follow-up were more likely to have remission than children who were wild type for rs1898671 (OR, 1.56; 95% CI, 1.26-1.91). In the second cohort (n = 585), the rs1898671 variant was less prevalent in those with AD than those without. The protective effect was greater in rs1898671 heterozygotes (OR, 1.91; 95% CI, 1.34-2.75) than homozygotes (OR, 1.28; 95% CI, 0.61-2.70).Conclusion: TSLP and specifically rs1898671 are important in the pathogenesis of AD and could represent a potential clinical target for the development of therapies to treat individuals with AD. (C) 2019 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
