Kawashima Kunihiro, Kishi Taro, Ikeda Masashi, Kitajima Tsuyoshi, Yamanouchi Yoshio, Kinoshita Yoko, Takahashi Nagahide, Saito Shinichi, Ohi Kazutaka, Yasuda Yuka, Hashimoto Ryota, Takeda Masatoshi, Inada Toshiya, Ozaki Norio, Iwata Nakao
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Am J Med Genet B Neuropsychiatr Genet. 2008 Oct 5;147B(7):1327-31. doi: 10.1002/ajmg.b.30781.
Abnormalities in neural connections and the neurotransmitter system appear to be involved in the pathophysiology of schizophrenia. The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, which consists of Syntaxin1A, vesicle-associated membrane protein 2 (VAMP2) and synaptosomal-associated protein 25 kDa (SNAP25), plays an important role in the neurotransmitter system, and is therefore an attractive place to search for candidate genes for schizophrenia. We conducted a two-stage genetic association analysis of Syntaxin1A (STX1A), VAMP2 and SNAP25 genes with schizophrenia (first-set screening samples: 377 cases and 377 controls, second-set confirmation samples: 657 cases and 527 controls). Based on the linkage disequilibrium, 40 SNPs (STX1A, 8 SNPs; VAMP2, 3 SNPs; SNAP25, 29 SNPs) were selected as 'tagging SNPs'. Only nominally significant associations of an SNP (rs12626080) and haplotype (rs363014 and rs12626080) in SNAP25 were detected in the first-set screening scan. To validate this significance, we carried out a replication analysis of these SNP and haplotype associations in second-set samples with a denser set of markers (including five additional SNPs). However, these associations could not be confirmed in the second-set analysis. These results suggest that the SNARE complex-related genes do not play a major role in susceptibility to schizophrenia in the Japanese population.
神经连接和神经递质系统的异常似乎与精神分裂症的病理生理学有关。可溶性N - 乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）复合体由Syntaxin1A、囊泡相关膜蛋白2（VAMP2）和突触体相关蛋白25 kDa（SNAP25）组成，在神经递质系统中起重要作用，因此是寻找精神分裂症候选基因的一个有吸引力的研究方向。我们对Syntaxin1A（STX1A）、VAMP2和SNAP25基因与精神分裂症进行了两阶段的基因关联分析（第一组筛查样本：377例患者和377例对照；第二组验证样本：657例患者和527例对照）。基于连锁不平衡，选择了40个单核苷酸多态性（SNPs）（STX1A有8个SNPs；VAMP2有3个SNPs；SNAP25有29个SNPs）作为“标签SNPs”。在第一组筛查扫描中，仅检测到SNAP25中一个单核苷酸多态性（rs12626080）和单倍型（rs363014和rs12626080）存在名义上显著的关联。为了验证这种显著性，我们在第二组样本中使用更密集的标记集（包括另外5个SNPs）对这些单核苷酸多态性和单倍型关联进行了重复分析。然而，在第二组分析中未能证实这些关联。这些结果表明，在日本人群中，SNARE复合体相关基因在精神分裂症易感性中不发挥主要作用。
