Functionality of promoter microsatellites of arginine vasopressin receptor 1A (AVPR1A): implications for autism

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.The neuropeptide arginine vasopressin (AVP) has been hypothesized to play a role in the aetiology of autism based on a demonstrated involvement in social bonding and in the regulation of a variety of socially relevant behaviours in animal models. Pharmacological experiments in rodents have shown a role for vasopressin in learning and memory, aggression and affiliative behaviours. Increases in AVP are associated with stressful or defensive circumstances and AVP is also involved in aggressive behaviours and pair bonding, mostly in males [1]. AVP regulates male social behaviour not just through higher expression in males but also in steroid-sensitive brain sexual dimorphisms in AVP neurons [1,2]. AVP may therefore influence sexually dimorphic social behaviours in a range of species [3]. The role of sex hormones on AVP is of interest in the context of autism considering that the ratio of affected males with autism compared to affected females is highly skewed (4:1) [4]. Only one study has examined the relationship between AVP levels and autism; Boso et al.