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NOS1 基因与日本人群甲基苯丙胺所致精神分裂症的关联分析

Genetic Association Analysis of NOS1 and Methamphetamine-Induced Psychosis Among Japanese.

机构信息

Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan.

出版信息

Curr Neuropharmacol. 2011 Mar;9(1):155-9. doi: 10.2174/157015911795017308.

Abstract

The neuronal nitric oxide synthase gene (NOS1) is located at 12q24, a susceptibility region for schizophrenia, and produces nitric oxide (NO). NO has been reported to play important roles as a gaseous neurotransmitter in brain. NO is a second messenger for the N-methyl-D aspartate (NMDA) receptor and is related to the dopaminergic system. Because the symptomatology of methamphetamine (METH) use disorder patients with psychosis is similar to that of patients with schizophrenia, NOS1 is a good candidate gene for METH-induced psychosis. Therefore, we conducted a case-control association study between NOS1 and METH-induced psychosis with Japanese subjects (183 with METH-induced psychosis patients and 519 controls). We selected seven SNPs (rs41279104, rs3782221, rs3782219, rs561712, rs3782206, rs6490121, rs2682826) in NOS1 from previous reports. Written informed consent was obtained from each subject. This study was approved by the Ethics Committee at Fujita Health University School of Medicine and each participating institute of the Japanese Genetics Initiative for Drug Abuse (JGIDA). No significant association was found between NOS1 and METH-induced psychosis in the allele/genotype-wise or haplotype-wise analyses. In conclusion, we suggest that NOS1 might not contribute to the risk of METH-induced psychosis in the Japanese population.

摘要

神经元型一氧化氮合酶基因(NOS1)位于 12q24,这是精神分裂症的易感区域,可产生一氧化氮(NO)。已有报道称,NO 作为一种气态神经递质在大脑中发挥重要作用。NO 是 N-甲基-D-天冬氨酸(NMDA)受体的第二信使,与多巴胺能系统有关。由于使用安非他命(METH)引起的精神病患者的症状与精神分裂症患者的症状相似,因此 NOS1 是 METH 引起的精神病的候选基因。因此,我们对日本受试者(183 名 METH 引起的精神病患者和 519 名对照)进行了 NOS1 与 METH 引起的精神病之间的病例对照关联研究。我们从先前的报告中选择了 NOS1 中的七个单核苷酸多态性(rs41279104、rs3782221、rs3782219、rs561712、rs3782206、rs6490121、rs2682826)。每位受试者均获得了书面知情同意。这项研究得到了藤田保健大学医学院伦理委员会和日本药物滥用遗传学倡议(JGIDA)各参与机构的批准。在等位基因/基因型或单体型分析中,NOS1 与 METH 引起的精神病之间没有发现显著的关联。总之,我们认为 NOS1 可能不会增加日本人群中 METH 引起的精神病的风险。

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