Noroozi Rezvan, Ghafouri-Fard Soudeh, Omrani Mir Davood, Habibi Mohsen, Sayad Arezou, Taheri Mohammad
Young Researchers and Elite Club, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran.
Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Gene. 2017 Aug 20;625:10-14. doi: 10.1016/j.gene.2017.05.003. Epub 2017 May 2.
Autism Spectrum Disorders (ASD) (MIM 209850) are a group of neurodevelopmental disorders distinguished by destructed social interaction and communication abilities along with peculiar repetitive behavior. Several genetic loci have been linked to this disorder. Vesicular monoamine transporter 1 (VMAT1/SLC18A1) is an attractive candidate gene for psychiatric disorders because of its participation in regulation monoamines. In the present case-control study, we evaluated the link between three non-synonymous single nucleotide polymorphisms (SNPs) (rs2270641 [Pro4Thr], rs2270637 [Thr98Ser] and rs1390938 [Thr136Ile]) and one intronic SNP (rs2279709) across the VMAT1 gene and ASD in a group of Iranian patients. Allele frequency analyses showed significant over-presentation of rs1390938-G allele in cases compared with controls (P<0.001). The analysis under different genetic models showed that the AA genotype of the rs1390938 was protective against ASD under dominant and recessive models. The rs2270641 SNP was associated with ASD risk only in over-dominant model. Other SNPs showed no significant difference in allele or genotype frequencies between two groups. Haplotype analysis revealed that C A T T and C A T G haplotypes (rs2270637, rs1390938, rs2279709 and rs2270641 respectively) have a protective effect against ASD. Consequently, the functional rs1390938 SNP in VMAT1 is associated with ASD in Iranian population. Considering the role of VMAT1 in regulation of monoamines, the dysregulated expression of this protein during early stages of brain development might be implicated in ASD.
自闭症谱系障碍（ASD）（MIM 209850）是一组神经发育障碍，其特征为社交互动和沟通能力受损以及存在特殊的重复行为。多个基因位点与该疾病相关。囊泡单胺转运体1（VMAT1/SLC18A1）因其参与单胺调节，是精神疾病的一个有吸引力的候选基因。在本病例对照研究中，我们评估了伊朗一组患者中VMAT1基因上的三个非同义单核苷酸多态性（SNP）（rs2270641 [Pro4Thr]、rs2270637 [Thr98Ser]和rs1390938 [Thr136Ile]）以及一个内含子SNP（rs2279709）与ASD之间的关联。等位基因频率分析显示，与对照组相比，病例组中rs1390938 - G等位基因显著过度出现（P<0.001）。不同遗传模型下的分析表明，rs1390938的AA基因型在显性和隐性模型下对ASD具有保护作用。rs2270641 SNP仅在超显性模型中与ASD风险相关。其他SNP在两组之间的等位基因或基因型频率上没有显著差异。单倍型分析显示，C A T T和C A T G单倍型（分别对应rs2270637、rs1390938、rs2279709和rs2270641）对ASD具有保护作用。因此，VMAT1中功能性的rs1390938 SNP与伊朗人群的ASD相关。考虑到VMAT1在单胺调节中的作用，该蛋白在大脑发育早期阶段的表达失调可能与ASD有关。
