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Although NT1 showed a strong association with human leukocyte antigen (<jats:italic>HLA<\/jats:italic>)<jats:italic>-DQB1*06:02<\/jats:italic>, the responsible antigens remain unidentified. We analyzed array-based DNA methylation and gene expression data for the <jats:italic>HLA<\/jats:italic> region in CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells that were separated from the peripheral blood mononuclear cells of Japanese subjects (NT1, N\u2009=\u200942; control, N\u2009=\u200942). As the large number of SNPs in the <jats:italic>HLA<\/jats:italic> 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\u2032 side of the probe, makes the probe unreliable. We confirmed that 90.3% of the probes after general filtering in the <jats:italic>HLA<\/jats:italic> 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 <jats:italic>HLA<\/jats:italic> class II region of the patients were significantly hypomethylated in CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells. This association was not detected when the effect of <jats:italic>HLA-DQB1*06:02<\/jats:italic> was considered, suggesting that the hypomethylation was possibly derived from <jats:italic>HLA-DQB1*06:02<\/jats:italic>. Further RNA sequencing revealed reduced expression levels of <jats:italic>HLA-DQB1<\/jats:italic> alleles other than <jats:italic>HLA-DQB1*06:02<\/jats:italic> in the patients with NT1. Our results suggest the involvement of epigenetic and expressional changes in <jats:italic>HLA-DQB1<\/jats:italic> in the pathogenesis of NT1.<\/jats:p>","DOI":"10.1038\/s41598-023-37511-4","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T09:02:37Z","timestamp":1687942957000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Narcolepsy type I-associated DNA methylation and gene expression changes in the human leukocyte antigen region"],"prefix":"10.1038","volume":"13","author":[{"given":"Kugui","family":"Yoshida-Tanaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihoko","family":"Shimada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Honda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsushi","family":"Tokunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Honda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Miyagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,28]]},"reference":[{"key":"37511_CR1","first-page":"24","volume-title":"HLA in Narcolepsy","author":"H Yutaka","year":"1988","unstructured":"Yutaka, H. 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None of the other authors have any financial conflicts of interest to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10464"}}