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GRM2 和 HTR2A 与日本人群中甲基苯丙胺所致精神病和精神分裂症的关联分析。

Association analysis of GRM2 and HTR2A with methamphetamine-induced psychosis and schizophrenia in the Japanese population.

机构信息

Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 2010 May 30;34(4):639-44. doi: 10.1016/j.pnpbp.2010.03.002. Epub 2010 Mar 6.

Abstract

BACKGROUND

Abnormalities in glutaminergic neural transmission have been suggested to be involved in the pathogenesis of schizophrenia. A recent study reported that alterations in the 5-HT2A-mGluR2 complex may be involved in neural transmission in the schizophrenic cortex. In addition, methamphetamine-induced psychosis is thought to be similar to schizophrenia. Therefore, we conducted a case-control study with Japanese samples (738 schizophrenia patients, 196 methamphetamine-induced psychosis patients, and 802 controls) to evaluate the association and interaction between GRM2, HTR2A and schizophrenia.

METHODS

We selected three 'tagging SNPs' in GRM2, and two biologically functional SNPs in HTR2A (T102C and A1438G), for the association analysis.

RESULTS

We detected a significant association between methamphetamine-induced psychosis and GRM2 in a haplotype-wise analysis, but not HTR2A. We did not detect an association between GRM2 or HTR2A and schizophrenia. In addition, no interactions of GRM2 and HTR2A were found in methamphetamine-induced psychosis or schizophrenia. We did not detect any novel polymorphisms in GRM2 when we performed a mutation search using methamphetamine-induced psychosis samples.

CONCLUSION

Our results suggested that GRM2 may play a role in the pathophysiology of methamphetamine-induced psychosis but not schizophrenia in the Japanese population. A replication study using larger samples or samples of other populations will be required for conclusive results.

摘要

背景

谷氨酸能神经传递异常被认为与精神分裂症的发病机制有关。最近的一项研究报告称,5-HT2A-mGluR2 复合物的改变可能与精神分裂症皮层的神经传递有关。此外,甲基苯丙胺引起的精神病被认为与精神分裂症相似。因此,我们进行了一项日本样本的病例对照研究(738 例精神分裂症患者、196 例甲基苯丙胺引起的精神病患者和 802 例对照),以评估 GRM2、HTR2A 与精神分裂症之间的关联和相互作用。

方法

我们选择了 GRM2 中的三个“标记 SNP”,以及 HTR2A 中的两个具有生物学功能的 SNP(T102C 和 A1438G),进行关联分析。

结果

我们在单体型分析中检测到甲基苯丙胺引起的精神病与 GRM2 之间存在显著关联,但与 HTR2A 无关。我们没有发现 GRM2 或 HTR2A 与精神分裂症之间存在关联。此外,在甲基苯丙胺引起的精神病或精神分裂症中,没有发现 GRM2 和 HTR2A 的相互作用。当我们使用甲基苯丙胺引起的精神病样本进行突变搜索时,没有发现 GRM2 中的任何新的多态性。

结论

我们的结果表明,GRM2 可能在日本人群中参与甲基苯丙胺引起的精神病的病理生理学,但不参与精神分裂症。需要使用更大的样本或其他人群的样本进行复制研究,以得出结论。

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