セロトニン神経系の遺伝子多型とフルボキサミンの抗うつ効果との関連性

• Project/Area Number: 13770536
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Psychiatric science
• Research Institution: Akita University
• Principal Investigator: 吉田 契造 秋田大学, 医学部, 助手 (60323151)
• Project Period (FY): 2001 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
• Keywords: antidepressant response / fluvoxamine / genetic polymorphism / major depressive disorder / nausea / selective serotonin reuptake inhibitor (SSRI) / fluvozamine / 5-HTT gene-linked polymorphic region / selective serotonin reuptake inhibitor / serotonin transporter

Research Abstract

セロトニントランスポーター(5-HTT)は選択的セロトニン再取り込み阻害剤(SSRI)の直接的な作用部位であり、セロトニン神経の遺伝子多型とSSRIの抗うつ効果との関連について関心が深まりつつある。我々は、54名の日本人大うつ病患者を対象として、セロトニン神経系の遺伝子多型((1)5-HTT gene-linked polymorphic region (5-HTTLPR),(2)a variable number of tandem repeat (VNTR)polymorphism in the second intron of the 5-HTT gene (STin2),(3)tryptophan hydroxylase (TPH) gene polymorphism in intron 7(TPH-A218C),(4)a functional polymorphism in the MAOA gene promoter(MAOA-VNTR),(5)-1438G/A polymorphism in the promoter region of the 5-HT2A gene)とfluvoxamineの抗うつ効果との関連を調査した。(1)の遺伝子多型では、responder群においてL型よりもS型の対立遺伝子頻度が有意に高かった。S型対立遺伝子を有する患者ではfluvoxamineの抗うつ作用が優れる可能性が示された。その他の遺伝子多型とfluvoxamineの臨床効果の間に有意な関連性は認められなかった。また、フルボキサミン投与中に発現する嘔気と(1)(2)(3)(4)遺伝子多型の関係について研究したが、有意な関連性は認められなかった。しかし、嘔気と(5)遺伝子多型との関係については有意な関連性が認められ、1型対立遺伝子を有する患者では3型対立遺伝子を有する患者よりも嘔気が出現しにくいことが示された。

Research Products

• [Publications] Yoshida, K., Ito, K., Sato, K.et al.: "Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients"Progress in Neuro-Psychopharmacology and Biological Psychiatry. 26. 383-386 (2002)
• [Publications] Yoshida, K., Naito, S., Takahashi, H.et al.: "Monoamine oxidase A gene polymorphism, tryptophan hydroxylase gene polymorphism and antidepressant response to fluvoxamine in Japanese patients with major depressive disorder"Progress in Neuro-Psychopharmacology and Biological Psychiatry. 26. 1279-1283 (2002)
• [Publications] Ito, K., Yoshida, K., Sato, K.et al.: "A Variable number of tandem repeats in the serotonin transporter gene does not affect the antidepressant response of fluvoxamine"Psychiatry Research. 111. 235-239 (2002)
• [Publications] Takahashi, H., Yoshida, K., Ito, K.et al.: "No association between the serotonergic polymorphisms and incidence of nausea induced by fluvoxamine treatment"European Neuropsychopharmacology. 12. 477-481 (2002)
• [Publications] Sato, K., Yoshida, K., Takahashi, H.et al.: "The Association between -1438G/A Promoter Polymorphism in the 5-HT_<2A> Receptor Gene and Fluvoxamine Response in Japanese Patients with Major Depressive Disorder"Neuropsychobiology. 46. 136-140 (2002)
• [Publications] Yoshida, K., Naito, S., Takahashi, H.et al.: "Monoamine oxidase A gene polymorphism, 5-HT_<2A> receptor gene polymorphism and incidence of nausea induced by fluvoxamine"Neuropsychobiology. 47(in press). (2003)
• [Publications] Yoshida K, Ito K, Sato K, Takahashi H, Higuchi H et al.: "Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients"Progress in Neuro-Psychopharmacology and Biological Psychiatry. 26. 383-386 (2002)