Association of HLA-DRB1 genetic variants with the persistence of atopic dermatitis.
Association of HLA-DRB1 genetic variants with the persistence of atopic dermatitis.
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DOI：
10.1016/j.humimm.2015.08.003
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发表时间：
2015-08
期刊：
影响因子：
2.7
通讯作者：
Kamoun M
中科院分区：
文献类型：
--
作者：
Margolis DJ;Mitra N;Kim B;Gupta J;Hoffstad OJ;Papadopoulos M;Wubbenhorst B;Nathanson KL;Duke JL;Monos DS;Kamoun M
特应性皮炎(AD)是一种儿童时期的疾病，可能是由于皮肤屏障改变和免疫失调之间的相互作用而引起的。我们研究的目的是利用全外显子组测序和高分辨率分型来评估DRB1基因变异与AD的持久性之间的关联。根据之前使用高吞吐量技术的报告对DRB1进行了询问。我们评估了一项正在进行的全国范围的AD儿童长期队列研究，其中患者每6个月被问及他们的药物使用情况和AD症状。总共有87名非洲裔美国儿童和50名欧洲裔美国儿童接受了评估。使用软件工具进行遗传关联分析，重点关注覆盖抗原提呈结构域的HLA-DRB1等位基因共享的氨基酸可变位。第9位(第9位)、第26位(第26位)和第78位(第4位)的氨基酸变异与AD的患病率略有关联。残基78的优势比为0.30(0.14，0.68；p=0.003)，残基26的优势比为0.27(0.10，0.69；p=0.006)，残基9对AD的持久性无显著意义。综上所述，在非裔美国儿童中，人类白细胞抗原-DRB1多肽结合区的氨基酸变异与AD的持久性有关。
Atopic dermatitis (AD) is a waxing and waning illness of childhood that is likely caused by interactions between an altered skin barrier and immune dysregulation. The goal of our study was to evaluate the association of DRB1 genetic variants and the persistence of AD using whole exome sequencing and high resolution typing. DRB1 was interrogated based on previous reports that utilized high throughput techniques. We evaluated an ongoing nation-wide long-term cohort of children with AD in which patients are asked every 6 months about their medication use and their AD symptoms. In total, 87 African-American and 50 European-American children were evaluated. Genetic association analysis was performed using a software tool focusing on amino acid variable positions shared by HLA-DRB1 alleles covering the antigen presenting domain. Amino acid variations at position 9 (pocket 9), position 26, and position 78 (pocket 4) were marginally associated with the prevalence of AD. However, the odds ratio was 0.30 (0.14, 0.68; p=0.003) for residue 78, 0.27 (0.10, 0.69; p=0.006) for residue 26 and not significant for residue 9 with respect to the persistence of AD. In conclusion, amino acid variations at peptide-binding pockets of HLA-DRB1 were associated with the persistence of AD in African-American children.