Department of Psychiatry, the First Teaching Hospital of Xinjiang Medical University, Urumqi.
J Clin Psychiatry. 2015 Jan;76(1):e76-82. doi: 10.4088/JCP.13m08962.
Synaptosomal-associated protein of 25 kDa (SNAP25) is a member of the soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) protein complex, which plays essential roles in the modulation of different voltage-gated calcium channels and neurotransmitter release. Many previous studies have reported the SNAP25 gene to be significantly associated with attention-deficit/hyperactivity disorder (ADHD). Recently, shared genetic variants have been demonstrated in 5 major psychiatric disorders, including schizophrenia, major depressive disorder, bipolar disorder, autism spectrum disorders, and ADHD. However, no compelling, convincing evidence has suggested an association between SNAP25 and schizophrenia or major depressive disorder. Thus, we investigated the association between SNAP25 and both schizophrenia and major depressive disorder in the Han Chinese population.
We performed a large-scale case-control study to test the association between SNAP25 and 2 major mental disorders, schizophrenia (DSM-IV criteria) and major depressive disorder (DSM-IV criteria), in the Han Chinese population. Seven single-nucleotide polymorphisms (SNPs) were genotyped in 1,330 schizophrenia patients, 1,045 major depressive disorder patients, and 1,520 healthy controls of Han Chinese origin.
Two SNPs, rs3787283 and rs3746544, were found to be associated with both schizophrenia (rs3746544, adjusted P = .00257) and major depressive disorder (rs3746544, adjusted P = .0485; rs3787283, adjusted P = .00387) in this study. The AG haplotype consisting of rs3787283 and rs3746544 was also significantly associated with both schizophrenia and major depressive disorder (schizophrenia: adjusted P = .0126; major depressive disorder: adjusted P = .000580). Additionally, we carried out a meta-analysis of the current data and published association results and further confirmed the association between rs3746544 and schizophrenia (Pmeta = .002, ORmeta = 1.213 [95% CI, 1.077-1.367]).
Our results indicated that SNPs in SNAP25 represented a common risk factor of both schizophrenia and major depressive disorder in the Han Chinese population.
突触相关蛋白 25kDa（SNAP25）是可溶性 N-乙基马来酰亚胺敏感因子附着受体（SNARE）蛋白复合物的成员，在调节不同电压门控钙通道和神经递质释放方面发挥着重要作用。许多先前的研究表明，SNAP25 基因与注意力缺陷/多动障碍（ADHD）显著相关。最近，在包括精神分裂症、重度抑郁症、双相情感障碍、自闭症谱系障碍和 ADHD 在内的 5 种主要精神疾病中，已经证明存在共享的遗传变异。然而，没有令人信服的证据表明 SNAP25 与精神分裂症或重度抑郁症之间存在关联。因此，我们在中国汉族人群中研究了 SNAP25 与精神分裂症和重度抑郁症之间的关联。
我们进行了一项大规模的病例对照研究，以检验 SNAP25 与精神分裂症（DSM-IV 标准）和重度抑郁症（DSM-IV 标准）这两种主要精神障碍在汉族人群中的关联。在 1330 名精神分裂症患者、1045 名重度抑郁症患者和 1520 名汉族健康对照中，共检测了 7 个单核苷酸多态性（SNP）。
在这项研究中，发现两个 SNP（rs3787283 和 rs3746544）与精神分裂症（rs3746544，调整后的 P =.00257）和重度抑郁症（rs3746544，调整后的 P =.0485；rs3787283，调整后的 P =.00387）均相关。由 rs3787283 和 rs3746544 组成的 AG 单倍型也与精神分裂症和重度抑郁症显著相关（精神分裂症：调整后的 P =.0126；重度抑郁症：调整后的 P =.000580）。此外，我们对当前数据和已发表的关联结果进行了荟萃分析，进一步证实了 rs3746544 与精神分裂症之间的关联（Pmeta =.002，ORmeta = 1.213 [95% CI，1.077-1.367]）。
我们的结果表明，SNAP25 中的 SNP 是汉族人群中精神分裂症和重度抑郁症的共同危险因素。
