Neuropsychiatric Genetics Research Group, Department of Psychiatry, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.
Mol Autism. 2011 Mar 31;2(1):3. doi: 10.1186/2040-2392-2-3.
Arginine vasopressin (AVP) has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. The arginine vasopressin receptor 1A gene (AVPR1A) is widely expressed in the brain and is considered to be a key receptor for regulation of social behaviour. Moreover, genetic variation at AVPR1A has been reported to be associated with autism. Evidence from non-human mammals implicates variation in the 5'-flanking region of AVPR1A in variable gene expression and social behaviour.
We examined four tagging single nucleotide polymorphisms (SNPs) (rs3803107, rs1042615, rs3741865, rs11174815) and three microsatellites (RS3, RS1 and AVR) at the AVPR1A gene for association in an autism cohort from Ireland. Two 5'-flanking region polymorphisms in the human AVPR1A, RS3 and RS1, were also tested for their effect on relative promoter activity.
The short alleles of RS1 and the SNP rs11174815 show weak association with autism in the Irish population (P = 0.036 and P = 0.008, respectively). Both RS1 and RS3 showed differences in relative promoter activity by length. Shorter repeat alleles of RS1 and RS3 decreased relative promoter activity in the human neuroblastoma cell line SH-SY5Y.
These aligning results can be interpreted as a functional route for this association, namely that shorter alleles of RS1 lead to decreased AVPR1A transcription, which may proffer increased susceptibility to the autism phenotype.
精氨酸加压素（AVP）被假设在自闭症的发病机制中起作用，基于其在调节社会行为方面的作用已得到证实。精氨酸加压素受体 1A 基因（AVPR1A）在大脑中广泛表达，被认为是调节社会行为的关键受体。此外，AVPR1A 中的遗传变异与自闭症有关。来自非人类哺乳动物的证据表明，AVPR1A 的 5'-侧翼区域的变异与可变基因表达和社会行为有关。
我们检查了 AVPR1A 基因中的四个标记单核苷酸多态性（SNP）（rs3803107、rs1042615、rs3741865、rs11174815）和三个微卫星（RS3、RS1 和 AVR），以研究它们在爱尔兰自闭症队列中的关联。还测试了人类 AVPR1A 中的两个 5'-侧翼区域多态性 RS3 和 RS1 对相对启动子活性的影响。
RS1 的短等位基因和 SNP rs11174815 与爱尔兰人群中的自闭症有微弱关联（分别为 P = 0.036 和 P = 0.008）。RS1 和 RS3 的长度均显示出相对启动子活性的差异。RS1 和 RS3 的较短重复等位基因降低了人神经母细胞瘤细胞系 SH-SY5Y 中的相对启动子活性。
这些一致的结果可以解释为这种关联的功能途径，即 RS1 的较短等位基因导致 AVPR1A 转录减少，这可能增加了对自闭症表型的易感性。
