THE AMYLOID RELATED TRANSTHYRETIN METABOLISM POST DOMINO LIVER TRANSPLANTATION

多米诺肝移植后淀粉样蛋白相关的甲状腺素蛋白代谢

• 批准号: 13670638
• 负责人: TAKEI Yo-ichi
• 金额: $ 2.18万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670638/
• 关键词: familial amyloid polyneuropathy; transthyretin; domino liver transplantation; mass spectrometry; transthyretin monomer; 肝移植; ドミノ移植; モノマー

We have diagnosed 20 familial amyloid polyneuropathy (FAP) patients and 5 FAP carriers since 2001. Most of these patients were diagnosed as having Val30Met transthyretin (TTR) mutation. We found a rare case with carpal tunnel syndrome and severe cardiac amyloidosis, whose ATTR Tyr69Ile was found to be caused by double-nucleotide substitution at codon 69.Twenty liver transplantations have been performed since 1993 in patients with FAP, including 5 domino liver transplantations. After the operation the serum concentration of mutant type TTR is increased promptly in domino recipients. Serial examinations of clinical findings and abdominal fat aspiration biopsy were performed for them after the operation. However, no sign of polyneuropathy, autonomic neuropathy and amyloid deposition was detected respectively. In FAP patients, mass spectrometry showed that the variant monomer was markedly decreased compared with the wild-type TTR monomer. In domino recipients who were transplanted FAP liver, variant monomer was not decreased. These findings suggest that the free variant TTR monomer is unstable in serum, and that it aggregates in deposits in various organs in FAP patients. However, in domino recipient amyloid deposition or amyloid fibril formation has not yet started within two or three years after operation. It is suggested that free variant TTR monomer is useful to know the beginning of amyloid deposition.

自2001年以来，我们已经诊断出20名家族性淀粉样蛋白多神经病（FAP）患者和5名FAP携带者。这些患者中的大多数被诊断为val30met transthyretin（TTR）突变。我们发现腕管综合征和严重心脏淀粉样变性的罕见病例，其Attryty69ile被发现是由CORDON 69的双核苷酸取代引起的。自1993年以来，对FAP患者进行了两种肝移植，其中包括5个多米诺骨牌肝移植。手术后，在多米诺骨牌受体中，突变体型TTR的血清浓度迅速增加。手术后，对临床发现和腹部脂肪抽吸活检进行了串行检查。然而，分别没有检测到多神经病，自主神经病和淀粉样蛋白沉积的迹象。在FAP患者中，质谱法显示，与野生型TTR单体相比，变体单体显着降低。在移植FAP肝脏的多米诺骨牌接受者中，变体单体并未减少。这些发现表明，自由变体TTR单体在血清中是不稳定的，并且它在FAP患者的各种器官的沉积物中汇总。但是，在多米诺骨牌受体中，淀粉样蛋白沉积或淀粉样蛋白原纤维的形成尚未在操作后两三年内开始。建议自由变体TTR单体知道知道淀粉样蛋白沉积的开始很有用。

项目成果

池田修一, 武井洋一, 服部健, 森田洋: "家族性アミロイドポリニューロパチー(FAP)肝移植後の末梢神経病変"末梢神経. 12(1). 45-48 (2001)

Shuichi Ikeda、Yoichi Takei、Ken Hattori、Hiroshi Morita：“肝移植后家族性淀粉样多发性神经病 (FAP) 周围神经病变”《周围神经》12(1)。

Owa M, Takei Y, Hashikura Y, Kawasaki S, Koyama M, Ikeda S: "Recurrent cerebral embolism in a familial amyloid polyneuropathy patient who received partial liver transplantation from a living donor."Intern Med. 40(3). 259-264 (2001)

Owa M、Takei Y、Hashikura Y、Kawasaki S、Koyama M、Ikeda S：“接受活体捐赠者部分肝移植的家族性淀粉样多发性神经病患者的复发性脑栓塞。”实习医生。

Takei Y.et al.: "Transthyretin Tyr69-to-Tle mutation (double-nucleotide substitution in codon 69) in a Japanese familial amyloidosis patient with cardiomyopathy and carpal tunnel syndrome"Amyloid : THE Journal of Protein Folding Disorders. (in press). (20

Takei Y.等人：“患有心肌病和腕管综合征的日本家族性淀粉样变性患者中的运甲状腺素蛋白 Tyr69-to-Tle 突变（密码子 69 中的双核苷酸替换）”淀粉样蛋白：蛋白质折叠疾病杂志。

Takei Y, Hattori T, Gono T, Tokuda T, Saitoh S, Hoshii Y, and Ikeda S.: "Senile systemic amyloidoeis presenting as bilateral carpal tunnel syndrome."Amyloid. 9(4). 252-255 (2002)

Takei Y、Hattori T、Gono T、Tokuda T、Saitoh S、Hoshii Y 和 Ikeda S.：“老年系统性淀粉样蛋白表现为双侧腕管综合征。”淀粉样蛋白。

Takei Y.et al.: "Senile systemic amyloidosis presenting as bilateral carpal tunnel syndrome"Amyloid : The Journal of Protein Folding Disorders. 9(4). 252-255 (2002)

Takei Y.等人：“表现为双侧腕管综合征的老年系统性淀粉样变性”淀粉样蛋白：蛋白质折叠疾病杂志。