2022 Fiscal Year Final Research Report

Identification of genes that influence methamphetamine toxicity and application to cause of death investigation

Research Project

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Project/Area Number	19K10698
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 58040:Forensics medicine-related
Research Institution	Fukuoka University
Principal Investigator	Matsusue Aya 福岡大学, 医学部, 講師 (70309920)
Co-Investigator(Kenkyū-buntansha)	久保真一福岡大学, 医学部, 教授 (10205122) 石川隆紀大阪公立大学, 大学院医学研究科, 教授 (50381984) 原健二福岡大学, 医学部, 講師 (00090738) 柏木正之福岡大学, 医学部, 准教授 (70301687) ウォーターズブライアン福岡大学, 医学部, 講師 (00609480) 高山みお福岡大学, 医学部, 講師 (40804802)
Project Period (FY)	2019-04-01 – 2023-03-31
Keywords	覚醒剤 / 遺伝子多型 / 剖検例
Outline of Final Research Achievements	Genes that may affect methamphetamine toxicity were examined in forensic autopsy cases. In men where methamphetamine was detected, no significant association was found between the VNTR polymorphism of the monoamine oxidase A gene and the levels of adrenaline, noradrenaline, and dopamine in the cerebrospinal fluid. We investigated the association between CYP2D6 gene polymorphism and body fluid methamphetamine concentration, amphetamine concentration, and metabolic ratio. Ultrarapid metabolizer, extensive metabolizer, intermediate metabolizer, and poor metabolizer phenotypes were predicted from CYP2D6 genotypes. The intermediate metabolizer showed an overall higher methamphetamine concentration than the extensive metabolizer. In particular, significant differences were observed in urine and bone marrow. Amphetamine concentrations and metabolic ratios were not significantly different in any body fluid.
Free Research Field	法医学
Academic Significance and Societal Importance of the Research Achievements	CYP2D6の遺伝子多型が、覚醒剤検出症例の体液中メタンフェタミン濃度に影響を与える可能性が示唆された。日本人では、CYP2D6の代謝能低下型の頻度が高い。代謝能低下型の場合、覚醒剤の体内濃度が正常型に比べて高くなり、覚醒剤の毒性も強く発現する可能性がある。申請者は、以前、覚醒剤摂取時の脳脊髄液中ドパミン濃度が、COMT遺伝子多型によって有意に上昇することを明らかにした。COMTと同様にカテコラミンの代謝に関わるMAOA遺伝子のVNTR多型を調べたが、男性における関連は認められなかった。