Resequencing of the entire HLA region in autoimmune liver diseases

自身免疫性肝病中整个 HLA 区域的重测序

• 批准号: 23590969
• 负责人: UMEMURA Takeji
• 金额: $ 3.41万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590969/
• 关键词: HLA; 自己免疫性肝炎; 原発性胆汁性肝硬変; 次世代シークエンサー; DNAタイピング

We investigated HLA class I A, B, and C and HLA class II DRB1 and DQB1 alleles and haplotypes in Japanese patients with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). HLA-DRB1 DRB1*04:05-DQB1*04:01 haplotype was significantly associated with AIH susceptibility. Conversely, the DRB1*15:01-DQB1*06:02 haplotype was associated with protection from both disease onset. Significant associations were found with PBC susceptibility for the DRB1*08:03-DQB1*06:01. There were significant protective associations with the DRB1*13:02-DQB1*06:04 and DRB1*11:01-DQB1*03:01 haplotypes. The frequency of the DRB1*08:03-DQB1*06:01 haplotype was significantly higher in AIH patients who developed hepatic failure. The frequency of the DRB1*09:01-DQB1*03:03 haplotype was significantly higher in PBC patients who had received orthotopic liver transplantation. We established the role of HLA haplotypes in determining AIH and PBC susceptibility, protection and progression in the Japanese population.

我们调查了日本自身免疫性肝炎（AIH）和原发性胆汁性肝硬化（PBC）患者的HLA I类A、B和C以及HLA II类DRB 1和DQB 1等位基因和单倍型。HLA-DRB 1 DRB 1 *04：05-DQB 1 *04：01单倍型与AIH易感性显著相关。相反，DRB 1 *15：01-DQB 1 *06：02单倍型与预防两种疾病发作相关。发现DRB 1 *08：03-DQB 1 *06：01与PBC易感性显著相关。DRB 1 *13：02-DQB 1 *06：04和DRB 1 *11：01-DQB 1 *03：01单倍型具有显著的保护性关联。DRB 1 *08：03-DQB 1 *06：01单倍型的频率在发生肝功能衰竭的AIH患者中显著较高。DRB 1 *09：01-DQB 1 *03：03单倍型在接受原位肝移植的PBC患者中的频率显著较高。我们在日本人群中建立了HLA单倍型在确定AIH和PBC易感性、保护和进展中的作用。

项目成果

STAT4 gene polymorphisms are associated with susceptibility and ANA status in primary biliary cirrhosis.

• DOI: 10.1155/2014/727393
• 发表时间: 2014
• 期刊: Disease markers
• 作者: Joshita S;Umemura T;Nakamura M;Katsuyama Y;Shibata S;Kimura T;Morita S;Komatsu M;Matsumoto A;Yoshizawa K;Ishibashi H;Tanaka E;Ota M
• 通讯作者: Ota M

Human leukocyte antigen class II haplotypes affect clinical characteristics and progression of type 1 autoimmune hepatitis in Japan.

• DOI: 10.1371/journal.pone.0100565
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Umemura T;Katsuyama Y;Yoshizawa K;Kimura T;Joshita S;Komatsu M;Matsumoto A;Tanaka E;Ota M
• 通讯作者: Ota M

Signal transducer and activator of transcription 4 gene polymorphisms are associated with production of anti-nuclear antibody in Japanese patients with primary biliary cirrhosis.

信号转导子和转录激活子4基因多态性与日本原发性胆汁性肝硬化患者抗核抗体的产生有关。

• 发表时间: 2012
• 作者: Joshita S;Umemura T;Nakamura M;Yoshizawa K;Katsuyama Y;Shibata S;Okuhara S;Nozawa Y ;Kimura T;Morita S;Komatsu M;Matsumoto A;Tanaka E;Ota M.
• 通讯作者: Ota M.

Association analysis of toll-like receptor 4 polymorphisms in Japanese primary biliary cirrhosis

• DOI: 10.1016/j.humimm.2012.10.022
• 发表时间: 2013-02-01
• 期刊: HUMAN IMMUNOLOGY
• 影响因子: 2.7
• 作者: Morita, Susumu;Joshita, Satoru;Ota, Masao
• 通讯作者: Ota, Masao

The future of Gastroenterology in Asia

亚洲胃肠病学的未来

• 发表时间: 2012
• 作者: 梅村武司、太田正穂(9名;9番);Umemura T
• 通讯作者: Umemura T