Department of Medical Genetics, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Department of Pediatrics, University of Tsukuba Hospital, Ibaraki, Japan.
Allergy. 2016 Oct;71(10):1486-9. doi: 10.1111/all.12950. Epub 2016 Aug 3.
This study investigated rare variants associated with atopic dermatitis. We performed exome analyses on 37 patients who were diagnosed with atopic dermatitis by board-certified dermatologists and had total serum IgE levels greater than 1000 IU/ml. The exome analysis identified seven variants with <1% allele frequency in Asian (ASN) population of 1000 Genomes Project phase 1 data and >5% allele frequency in the atopic dermatitis exome samples. We then conducted a replication study using 469 atopic dermatitis patients with total serum IgE ≥1000 IU/ml and 935 Japanese controls to assess the presence of these 7 candidate variants. The replication study confirmed that CYP27A1 rs199691576 (A/G) was associated with atopic dermatitis with high serum IgE levels (P = 0.012, odds ratio = 2.1). CYP27A1 is involved in the metabolism of vitamin D3, which plays important roles in modulating immune function. Previous studies have reported polymorphisms in vitamin D pathway genes that are associated with allergy-related phenotypes. Our data confirm the importance of genes regulating the vitamin D pathway in the development of atopic dermatitis.
本研究调查了与特应性皮炎相关的罕见变异。我们对 37 名经董事会认证的皮肤科医生诊断为特应性皮炎且总血清 IgE 水平大于 1000IU/ml 的患者进行了外显子组分析。外显子组分析在亚洲（ASN）1000 基因组项目第 1 阶段数据中发现了 7 个罕见变异，其等位基因频率<1%，在特应性皮炎外显子组样本中频率>5%。然后，我们使用总血清 IgE≥1000IU/ml 的 469 名特应性皮炎患者和 935 名日本对照进行了复制研究，以评估这 7 个候选变异的存在。复制研究证实，CYP27A1 rs199691576（A/G）与高血清 IgE 水平的特应性皮炎相关（P=0.012，优势比=2.1）。CYP27A1 参与维生素 D3 的代谢，维生素 D3 在调节免疫功能方面发挥重要作用。先前的研究报告了与过敏相关表型相关的维生素 D 途径基因的多态性。我们的数据证实了调节维生素 D 途径的基因在特应性皮炎发展中的重要性。
