Association analysis of the glutamic acid decarboxylase 2 and the glutamine synthetase genes (GAD2, GLUL) with schizophrenia
Association analysis of the glutamic acid decarboxylase 2 and the glutamine synthetase genes (GAD2, GLUL) with schizophrenia
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DOI：
10.1097/ypg.0b013e328311875d
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发表时间：
2009-02-01
影响因子：
0.9
通讯作者：
Fukumaki, Yasuyuki
中科院分区：
文献类型：
--
作者：
Arai, Shinsaku;Shibata, Hiroki;Fukumaki, Yasuyuki
目的谷氨酸能神经递质系统功能障碍是精神分裂症发病机制的一个可能假说，谷氨酸能神经递质系统相关基因是精神分裂症易感基因。本研究的目的是阐明编码谷氨酸代谢酶的两个基因的贡献：谷氨酸脱羧酶2基因（GAD 2）和谷氨酰胺合成酶基因（GLUL），方法我们对300名日本精神分裂症患者和300名健康对照者进行GAD 2基因的14个单核苷酸多态性（SNP）基因分型，（大小约91 kb）和GLUL中的6个SNP（大小约14 kb）。我们研究了“单点”关联以及成对单体型关联的所有SNPs与schizophrenia.Results我们没有观察到显着的“单点”关联与疾病的任何20个SNPs校正后的多重测试使用错误发现率。我们还观察到单倍型与错误发现率没有显著关联。此外，我们分析了基因-基因相互作用，包括六个谷氨酸受体基因，我们已经报告了先前的关联研究GRIA 4，GRIN 2D，GRIK 3，GRIK 4，GRIK 5，GRM 3，使用多因素降维方法。最好的相互作用模型，但是，没有显示出统计学显着性。结论这些结果表明，GAD 2和GLUL不发挥主要作用，精神分裂症的发病机制，并没有在日本人群中的8个基因之间的基因-基因相互作用。Psychiatr Genet 19：6-13（C）2009 Wolters Kluwer Health vertical bar Lippincott威廉姆斯& Wilkins.
Objective As dysfunction of glutamatergic neurotransmission is one of the plausible hypotheses for the pathogenesis of schizophrenia, genes involved in the glutamate neurotransmitter system are candidates for schizophrenia susceptibility. The aim of this study is to clarify the contribution of two genes encoding glutamate metabolic enzymes: the glutamic acid decarboxylase 2 gene (GAD2) and the glutamine synthetase gene (GLUL), in schizophrenia.Methods We genotyped 300 Japanese schizophrenia patients and 300 healthy controls for 14 single nucleotide polymorphisms (SNPs) in GAD2 (approximately 91 kb in size) and six SNPs in GLUL (approximately 14 kb in size). We examined 'single-point' association as well as pairwise haplotype association for all SNPs with schizophrenia.Results We observed no significant 'single-point' associations with the disease in any of the 20 SNPs after correction for multiple testing using False Discovery Rate. We also observed no significant haplotype associations with False Discovery Rate. Furthermore, we analyzed gene-gene interactions, including six glutamate receptor genes we have reported previously in the association studies of GRIA4, GRIN2D, GRIK3, GRIK4, GRIK5, and GRM3, using the multifactor dimensionality reduction method. The best interaction model, however, did not show the statistical significance.Conclusion These results suggest that GAD2 and GLUL do not play a major role in schizophrenia pathogenesis and there is no gene-gene interaction between the eight genes in the Japanese population. Psychiatr Genet 19:6-13 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.