Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
Curr Neuropharmacol. 2011 Mar;9(1):160-2. doi: 10.2174/157015911795017001.
Several investigations have suggested that abnormalities in glutamate neural transmission play a role in the pathophysiology of psychiatric disorders, including schizophrenia. The metabotropic glutamate 3 receptor (mGluR3) gene was reported to be associated with schizophrenia, and paranoid type schizophrenia has symptoms that are similar to those of methamphetamine-induced psychosis. This suggests that mGluR3 gene (GRM3) is a good candidate gene for the pathogenesis of methamphetamine-induced psychosis. To evaluate the association between GRM3 and methamphetamine-induced psychosis, we conducted a case-control study of Japanese samples (181 methamphetamine-induced psychosis and 232 controls).
We selected one functional SNP (rs6465084), reported to be associated with prefrontal brain functioning, for an association analysis. Written informed consent was obtained from each subject. This study was approved by the ethics committees at Fujita Health University, Nagoya University Graduate School of Medicine and each participating member of the Institute of the Japanese Genetics Initiative for Drug Abuse (JGIDA).
We did not detect an association between rs6465084 in GRM3 and Japanese methamphetamine-induced psychosis.
Our findings suggest that rs6465084 in GRM3 does not play a major role in the pathophysiology of methamphetamine-induced psychosis in the Japanese population. However, because we did not perform an association analysis based on linkage disequilibrium (LD) or a mutation scan of GRM3, a replication study using a larger sample and based on LD may be required for conclusive results.
几项研究表明，谷氨酸神经传递异常在精神疾病的病理生理学中起作用，包括精神分裂症。代谢型谷氨酸受体 3（mGluR3）基因与精神分裂症有关，偏执型精神分裂症的症状与甲基苯丙胺引起的精神病相似。这表明 mGluR3 基因（GRM3）是甲基苯丙胺引起的精神病发病机制的候选基因。为了评估 GRM3 与甲基苯丙胺引起的精神病之间的关系，我们对日本样本（181 例甲基苯丙胺引起的精神病和 232 例对照）进行了病例对照研究。
我们选择了一个与前额叶脑功能相关的功能性 SNP（rs6465084）进行关联分析。每个受试者都获得了书面知情同意。本研究得到了藤田保健大学、名古屋大学研究生院医学部和日本药物滥用遗传学倡议研究所（JGIDA）每个成员的伦理委员会的批准。
我们没有发现 GRM3 中的 rs6465084 与日本甲基苯丙胺引起的精神病之间存在关联。
我们的研究结果表明，GRM3 中的 rs6465084 并不在日本人群中发挥主要作用甲基苯丙胺引起的精神病的病理生理学。然而，由于我们没有根据连锁不平衡（LD）或 GRM3 的突变扫描进行关联分析，因此可能需要使用更大的样本并基于 LD 进行复制研究以获得结论性结果。
