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論文
- タイトル
- タイトル（英）
- Narcolepsy type I-associated DNA methylation and gene expression changes in the human leukocyte antigen region.
- 参照URL
- https://researchmap.jp/geogeo/published_papers/42792984
- 著者
- 著者（英）
- Kugui Yoshida-Tanaka,Mihoko Shimada,Yoshiko Honda,Akihiro Fujimoto,Katsushi Tokunaga,Makoto Honda,Taku Miyagawa
- 担当区分
- 最終著者
- 概要
- 概要（英）
- Narcolepsy type 1 (NT1) is caused by a loss of hypothalamic orexin-producing cells, and autoreactive CD4+ and CD8+ T cells have been suggested to play a role in the autoimmune mechanism. Although NT1 showed a strong association with human leukocyte antigen (HLA)-DQB1*06:02, the responsible antigens remain unidentified. We analyzed array-based DNA methylation and gene expression data for the HLA region in CD4+ and CD8+ T cells that were separated from the peripheral blood mononuclear cells of Japanese subjects (NT1, N = 42; control, N = 42). As the large number of SNPs in the HLA region might interfere with the affinity of the array probes, we conducted a comprehensive assessment of the reliability of each probe. The criteria were based on a previous study reporting that the presence of frequent SNPs, especially on the 3' side of the probe, makes the probe unreliable. We confirmed that 90.3% of the probes after general filtering in the HLA region do not include frequent SNPs, and are thus suitable for analysis, particularly in Japanese subjects. We then performed an association analysis, and found that several CpG sites in the HLA class II region of the patients were significantly hypomethylated in CD4+ and CD8+ T cells. This association was not detected when the effect of HLA-DQB1*06:02 was considered, suggesting that the hypomethylation was possibly derived from HLA-DQB1*06:02. Further RNA sequencing revealed reduced expression levels of HLA-DQB1 alleles other than HLA-DQB1*06:02 in the patients with NT1. Our results suggest the involvement of epigenetic and expressional changes in HLA-DQB1 in the pathogenesis of NT1.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Scientific reports
- 巻
- 13
- 号
- 1
- 開始ページ
- 10464
- 終了ページ
- 10464
- 出版年月
- 2023年6月28日
- 査読の有無
- 査読有り
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1038/s41598-023-37511-4
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