Functionality of promoter microsatellites of arginine vasopressin receptor 1A (AVPR1A): implications for autism
Year: 2011
Type: article
Study design: Observational Study
Abstract: BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Source: Molecular Autism
Institution: Trinity College Dublin
Language: English
Subfield: Social Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: gold
Estimated APC paid: $3,990
Funders: Wellcome Trust, Health Research Board
OpenAlex ID: W2170048523