悪性症候群とチトクロームP450:悪性症候群の発症・病態に関する分子遺伝学的研究

恶性综合征与细胞色素P450：恶性综合征发病和病理的分子遗传学研究

• 批准号: 12770541
• 负责人: 河西 千秋
• 金额: $ 1.47万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Encouragement of Young Scientists (A)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12770541/
• 关键词: CYP2D6; debrisoquine4-hydioxylase; (抗精神病薬)neuroleptics; 悪性症候群; 薬理遺伝学; 遺伝子; 副作用

本年度は,悪性症候群に罹患した症例を36名登録し,精神科診断,合併症,病歴,治療歴,治療反応性,悪性症候群発症時の状況など種々の情報を元にデータベースを作成した.その上で,各症例についてチトクロームP4502D6(CYP2CD6)遺伝子の変異と遺伝子型を調べた.CYP2CD6^*10変異アレルの検出には著者らが既述した方法(Kawanishi et al.,J Neurol Sci,160,102,1998)に基きPCR法とRFLPを用いた,また遺伝子の全欠損の検出にはJohanssonら(Pharmacogeret6,351,1996),Aklilluら(JPharmacol Exp Ther,278,441,1996)の方法に基づきLongPCR法を用いた.得られた結果は対照(抗精神病薬の内服を2年以上行いかつ悪性症候群に罹患したことのない精神分裂病症例)と比較し,統計的解析を行い検討した.悪性症候群症例36例のうち29例は原疾患が精神分裂病であった.悪性症候群起因薬剤のうち最も頻度が高いのはハロペリドールで,少なくとも10例で悪性症候群発症との関連が疑われた.悪性症候群罹患者では^*10変異アレルの頻度は41.7%で,ホモ接合体は25%であった.アレル,遺伝子型ともに対照と比較して有意差は認めなかった.悪性症候群の症例では全欠損の症例は認めなかった.結果の一部はPsychiatric Geneteics誌に報告した(Kawanishi et al.,Psychiatric Genet,10,145,2000).今後はさらに悪性症候群の症例数を集積し,データを蓄積した上で解析を行うとともに,症例個々において変異の有無/遺伝子型と,症状の多様性,重篤度,経過などについて詳細に検討を行う予定である.

This year, 36 cases of sexual syndrome were registered. Psychiatric diagnosis, comorbidities, disease history, treatment history, treatment of sexual syndrome. In this paper, we describe the method of P4502D6 (CYP2CD6) gene mutation and its subtype in each case. CYP2CD6 ^*10 gene mutation and its subtype mutation (Kawanishi et al., J Neurol Sci,160,102,1998), J Neurol Exp Ther,278,441, 1996), J Neurol Sci, 160, 102, 1998). The results were compared (antipsychotic drugs taken orally for more than 2 years, schizophrenia syndrome cases) and analyzed statistically. There were 36 cases of schizophrenia syndrome and 29 cases of schizophrenia. The most frequent cause of sexual syndrome was found in 10 cases, and the most frequent cause of sexual syndrome was found in 10 cases. The frequency of sex syndrome was 41.7%, and the frequency of sex syndrome was 25%. The difference between the two is that they are different. The symptoms of sexual syndrome are completely deficient. A report on Psychiatric Genetics (Kawanishi et al., Psychiatric Genet,10,145,2000). In the future, the number of cases of sexual syndrome will be accumulated, the number of cases will be accumulated, the number of cases will be analyzed, the number of cases will be different, and the number of cases will be different.

项目成果

Chiaki Kawanishi et al.: "Lack of association in Japanese patients between neuroleptic malignant syndrome and a debrisoquine 4-hydroxylase genotype with low enzyme activity"Psychiatric Genetics. 10. 145-147 (2000)

Chiaki Kawanishi 等人：“日本患者中抗精神病药恶性综合征与酶活性低的异喹啉 4-羟化酶基因型之间缺乏关联”精神病遗传学。