Safari Mohammad Reza, Omrani Mir Davood, Noroozi Rezvan, Sayad Arezou, Sarrafzadeh Shaghayegh, Komaki Alireza, Manjili Fateme Asadzadeh, Mazdeh Mehrdokht, Ghaleiha Ali, Taheri Mohammad
Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Mol Neurosci. 2017 Mar;61(3):305-311. doi: 10.1007/s12031-016-0860-2. Epub 2016 Nov 26.
Autism spectrum disorder (ASD) is a common, complex neurological condition, affecting approximately 1% of people worldwide. Monogenic neurodevelopmental disorders which showed autistic behavior patterns have suggested synaptic dysfunction, as a key mechanism in the pathophysiology of ASD. Subsequently, genes involved in synaptic signaling have been investigated with a priority for candidate gene studies. A synaptosomal-associated protein 25 (SNAP25) gene plays a crucial role in the central nervous system, contributing to exocytosis by targeting and fusion of vesicles to the cell membrane. Studies have shown a correlation between aberrant expression of the SNAP25 and a variety of brain diseases. Single nucleotide polymorphisms (SNPs) in this gene are associated with several psychiatric diseases, such as bipolar, schizophrenia, and attention-deficit/hyperactivity disorder. The aim of the present study was to investigate whether polymorphisms (rs3746544 and rs1051312) in the regulatory 3'-untranslated region (3'UTR) of the SNAP25 gene have an association with ASD in unrelated Iranian case (N = 524)-control (N = 472) samples. We observed robust association of the rs3746544 SNP and ASD patients, in both allele and haplotype-based analyses. Our results supported the previous observations and indicated a possible role for SNAP25 polymorphisms as susceptibility genetic factors involved in developing ASD.
自闭症谱系障碍（ASD）是一种常见的复杂神经疾病，全球约1%的人受其影响。表现出自闭行为模式的单基因神经发育障碍提示突触功能障碍是ASD病理生理学的关键机制。随后，参与突触信号传导的基因成为候选基因研究的重点。突触体相关蛋白25（SNAP25）基因在中枢神经系统中起关键作用，通过将囊泡靶向并融合到细胞膜来促进胞吐作用。研究表明，SNAP25的异常表达与多种脑部疾病相关。该基因的单核苷酸多态性（SNP）与几种精神疾病有关，如双相情感障碍、精神分裂症和注意力缺陷多动障碍。本研究的目的是调查SNAP25基因调控性3'非翻译区（3'UTR）中的多态性（rs3746544和rs1051312）与伊朗无关病例（N = 524）-对照（N = 472）样本中的ASD是否存在关联。在基于等位基因和单倍型的分析中，我们观察到rs3746544 SNP与ASD患者之间存在显著关联。我们的结果支持了先前的观察结果，并表明SNAP25多态性作为参与ASD发生的易感遗传因素可能发挥的作用。
