Examination of AVPR1a as an autism susceptibility gene

Abstract

Impaired reciprocal social interaction is one of the core features of autism. While its determinants are complex, one biomolecular pathway that clearly influences social behavior is the arginine-vasopressin (AVP) system. The behavioral effects of AVP are mediated through the AVP receptor 1a (AVPR1a), making the AVPR1a gene a reasonable candidate for autism susceptibility. We tested the gene's contribution to autism by screening its exons in 125 independent autistic probands and genotyping two promoter polymorphisms in 65 autism affected sibling pair (ASP) families. While we found no nonconservative coding sequence changes, we did identify evidence of linkage and of linkage disequilibrium. These results were most pronounced in a subset of the ASP families with relatively less severe impairment of language. Thus, though we did not demonstrate a disease-causing variant in the coding sequence, numerous nontraditional disease-causing genetic abnormalities are known to exist that would escape detection by traditional gene screening methods. Given the emerging biological, animal model, and now genetic data, AVPR1a and genes in the AVP system remain strong candidates for involvement in autism susceptibility and deserve continued scrutiny. Molecular Psychiatry (2004) 9, 968-972.

Association between the arginine vasopressin 1a receptor (AVPR1a) gene and autism in a family-based study: mediation by socialization skills

“…For RS1, nine alleles (308-340) were identified and the distribution of allele frequencies is similar to previous reports. 6,7 For RS3, 16 alleles (318-350 bp) were identified and the distribution of allele frequencies is similar to a previous report. 5 …”

“…3 Intriguingly, in humans, similar repetitive regions have been identified in the promoter region (RS1 and RS3) as well as in the single intron (AVR), although the role of these repeat regions in receptor expression remains to be elucidated. 4,5 Recently, two independent reports demonstrated provisional association between microsatellites (RS1, RS3) in the promoter region of AVPR1a and autistic disorder 6,7 and we observed association between these microsatellites and social behavior in a nonclinical population of university students. 8 These first studies are of special interest because social communication and social interaction are among the core deficits of autistic disorder.…”

“…Additionally, the location of AVPR1a on chromosome 12q14-15 is also a site for linkage to autistic disorder in at least one genome scan. 7 It is worth considering that in human's, as in rodents, this gene contributes to the genetic underpinnings of the social brain and may contribute to disorders characterized by a deficit in social cognition. Overall, these findings suggest that the AVPR1a gene is a worthwhile candidate for further investigation in autistic disorder, prompting us in the current study to attempt to confirm as well as extend these first findings by gentoyping three microsatellites (two promoter and one intronic) in the AVPR1a receptor gene in 116 families (128 probands) for association with autism using a robust family-based design.…”

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

“…Additionally, SNPs associated with ASD are also associated with amygdala volume [29], depression/anxiety [29], negative emotionality [30], attention deficit [31], adult attachment styles [32,33] (but see [34]), affectivity, emotional loneliness and IQ [35], empathy and stress reactivity [36], observed parenting [37], with sexual phenotypes [38] and in our own studies with prosocial behavior [39]. Interestingly, the AVPR1a receptor of the closely related nonapeptide vasopressin has also been associated with ASD [40][41][42]. This provisional role of OT in ASD, is further supported by two linkage studies [43,44], clinical evidence by several groups demonstrating clinical improvement in ASD following OT administration [45][46][47][48][49][50][51] (also see [52,53]) and studies showing that ASD is also associated with alterations in OT plasma levels [54].…”

Association of the arginine vasopressin receptor 1A (AVPR1A) haplotypes with listening to music

“…[4][5] The arginine vasopressin receptor 1A gene (AVPR1A) encodes for a receptor molecule, a neuropeptide that mediates the influences of the AVP hormone in the brain. 6 AVP has an important role in memory and learning. 7 AVPR1A has been shown to modulate social cognition and behavior, including attachment, social bonding and altruism in humans and other species.…”