再生不良性貧血における連鎖解析を用いた疾患感受性遺伝子の同定

利用连锁分析鉴定再生障碍性贫血的疾病易感基因

• 批准号: 18790648
• 负责人: 杉盛 千春
• 金额: $ 2.18万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18790648/
• 关键词: 再生不良性貧血; HLA; 発作性夜間血色素尿症; マイクロサテライト; 疾患感受性遺伝子; ヒト白血球抗原(HLA); PNH; 相関解析

再生不良性貧血(再不貧)患者ではHLA-DRB1*1501アレルとHLA-DRB1*1502アレルを保有する患者が多く、発作性夜間血色素尿症(PNH)型血球が高率に検出されることが知られている。このPNH型血球は再不貧の病態に免疫学的異常が関与している事の証拠とされているが、HLA-DRB1*1501患者ではPNH型血球の微少増加が高率に検出され、均一な疾患像を呈する一方、HLA-DRB1*1502患者ではPNH型血球陰性例も多い。このことからHLA-DRB1*1501アレルHLA-DRB1*1502アレルはわずか1アミノ酸の違いながら再不貧の病態に果たす役割は異なっている可能性が考えられた。HLA-DRB1*1501患者保有患者と比較して検討した結果、HLA-DR15分子の抗原提示とは無関係の真の疾患感受性遺伝子がHLA-DRB1*1502の近傍に存在する可能性が考えられた。そこで、本研究ではHLA-DRB1*1502を保有するPNH型血球陽性および陰性のそれぞれの患者群を対象としてマイクロサテライトマーカーを用いた相関解析を行い、両群間で頻度が大きく異なるマイクロサテライトマーカーを同定することによりHLA-DRB1*1502に連鎖したPNH型血球陰性再不貧の疾患感受性遺伝子の同定を目指した。62例のHLA-DRB1*1502陽性再不貧患者(PNH型血球陽性患者37例、PNH型血球陰性患者25例)についてマイクロサテライトマーカーを用いた相関解析行った結果、PNH型血球陰性HLA-DRB1*1502陽性再不貧患者ではC1-3-1の293アレルの頻度が有意に高かった(33% vs 3%, Pc=0.03)。一方、PNH型血球陽性HLA-DRB1*1502陽性再不貧患者では同部位のアレル頻度に差は見られなかった。この事から、PNH型血球陰性HLA-DRB1*1502陽性再不貧患者ではC1-3-1近傍のOct-4などのいくつかの疾患感受性候補遺伝子が同定された。

Patients with regenerative dysplastic blood (no more) were diagnosed as having multiple and paroxysmal nocturnal hemoglobinuria (PNH) in patients with multiple and paroxysmal nocturnal hemoglobinuria (PNH). The rate of HLA-DRB1*1501 infection was higher than that of normal controls. The number of PNH type blood cells in patients with HLA-DRB1*1501 is no longer normal and abnormal in immunology. The number of PNH blood cells in patients with PNH is small, and the number of PNH blood cells in patients with PNH is small, and the number of PNH blood cells in patients with HLA-DRB1*1502 is higher than that in patients with PNH. I don't know what to do. I don't know. I don't know what's going on. Patients with HLA-DRB1*1501 retain the results of patient comparison test results, and HLA-DR15 molecular antigen indicates that there is a possibility that there is a close proximity to the susceptibility to disease, HLA-DRB1*1502, and so on. In this study, the blood cells of PNH type were kept in the HLA-DRB1*1502, and the patients were divided into two groups: the patients were divided into two groups. There is a high degree of sensitivity between groups. The same number of samples were detected in the same group as those in the control group. The PNH type blood cells were no longer affected by the disease susceptibility test. The target index was the same. A total of 62 patients with HLA-DRB1*1502 dysmenorrhea (37 patients with PNH and 25 patients with PNH) were enrolled in this study. the results were analyzed by phase analysis, and the results were analyzed by phase analysis. the patients with sexual HLA-DRB1*1502 of PNH were intentionally high (33% vs 3%, Pc=0.03). One side, PNH blood cell sexual HLA-DRB1*1502 sex is no longer in the same part of the patient, there is a difference in the degree of sex in the same site. The patients with sexual HLA-DRB1*1502 of PNH and PNH blood cells no longer have sex. C1-3-1 is close to Oct-4.

项目成果

Cyclosporine Therapy for Acquired Aplastic Anemia: Predictive Factors for the Response and Long-term Prognosis

• DOI: 10.1532/ijh97.06156
• 发表时间: 2007-04
• 期刊: International Journal of Hematology
• 影响因子: 2.1
• 作者: H. Yamazaki;C. Sugimori;T. Chuhjo;S. Nakao

末梢血PNH型血球の意義

外周血PNH型血细胞的意义

• 发表时间: 2007
• 作者: Okumura;H.;et. al.;Chiharu Sugimori;Hideyuki Takamatsu;Shinji Nakao;杉盛 千春
• 通讯作者: 杉盛 千春

Graft rejection and hyperacute graft-versus-host disease in stem cell transplantation from non-inherited maternal-antigen-com

非遗传性母体抗原干细胞移植中的移植排斥和超急性移植物抗宿主病

• 发表时间: 2007
• 期刊: European Journal of Hematology 78
• 作者: Okumura;H.;et. al.
• 通讯作者: et. al.

Clinical significance of small population of paroxysmal nocturnal hemoglobinuria-type cells in the management of bone marrow failure.

小群阵发性睡眠性血红蛋白尿型细胞在骨髓衰竭治疗中的临床意义。

• 发表时间: 2006
• 期刊: International journal of Hematoloty 84・2
• 作者: Okumura;H.;et. al.;Chiharu Sugimori;Hideyuki Takamatsu;Shinji Nakao
• 通讯作者: Shinji Nakao

Specific antibodies to moesin, a membrane-cytoskelton linker protein, are frequently detected in patients with acquired aplastic anemia.

莫斯蛋白（一种膜细胞骨架连接蛋白）的特异性抗体，经常在患有获得性再生障碍性贫血的患者中检测到。

• 发表时间: 2007
• 期刊: Blood 109・6
• 作者: Okumura;H.;et. al.;Chiharu Sugimori;Hideyuki Takamatsu
• 通讯作者: Hideyuki Takamatsu