Journal of Molecular Neuroscience

, Volume 65, Issue 2, pp 213–221 | Cite as

Evidence for Association Between OXTR Gene and ASD Clinical Phenotypes

  • Lucas de Oliveira Pereira Ribeiro
  • Pedro Vargas-Pinilla
  • Djenifer B. Kappel
  • Danae Longo
  • Josiane Ranzan
  • Michele Michelin Becker
  • Rudimar dos Santos Riesgo
  • Lavinia Schuler-Faccini
  • Tatiana Roman
  • Jaqueline Bohrer SchuchEmail author


Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder characterized by impairments in social behaviors and communication. Oxytocin and its signaling pathway are related to a range of human behaviors, from facial expression recognition to aggressive behaviors, and have been suggested as involved in the etiology of ASD. Our aim was to evaluate the influence of two polymorphisms (rs1042778, rs53576) at the oxytocin receptor gene (OXTR) on ASD diagnosis and on specific ASD-related clinical symptoms (seizures, panic, and aggressive behaviors). We also assessed if these SNPs could be related to changes in OXTR availability and functionality using a bioinformatic approach. The sample was composed by 209 probands with ASD and their biological parents. Family-based approach and logistic regression models were used to investigated the outcomes. We observed that panic and aggressive behaviors were nominally associated with presence of rs1042778 T allele (P = 0.019/Pcorr = 0.114; P = 0.046/Pcorr = 0.276 respectively). Also, in the family-based analysis, a trend towards association with ASD susceptibility was observed for rs1042778 (G allele) (P = 0.066). In a bioinformatic approach, we demonstrated that rs1042778 G allele is determinant for the binding of the transcription factor MAZ, suggesting that when the T allele is present, the absence of MAZ binding might be associated with lower transcription levels of the OXTR gene. The overall findings suggest that the OXTR gene may play a role in ASD diagnosis and some of its clinical phenotypes, supported by previous animal and clinical studies. Further investigations are necessary to replicate our findings and fully understand the effects of the oxytocin pathway on ASD.


Autism Oxytocin receptor gene Panic Aggressive Oxytocin Endophenotype 



We are grateful to all clinical staff at the Child Neurology Unit and technicians at the Laboratory of Biological Samples Collection from Hospital de Clínicas de Porto Alegre for their assistance with clinical data and blood sample collections, respectively. We also thank Dr. Sandra Leistner-Segal at the Medical Genetics Service from Hospital de Clínicas de Porto Alegre for the fragile X syndrome genotyping. We lastly would like to thank all the families who kindly participated in this research.

Funding Information

The study was funded by the following the institutions: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundo de Incentivo a Pesquisa e Eventos – Hospital de Clínicas de Porto Alegre (FIPE-HCPA), and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS).

Compliance with Ethical Standards

This study was approved by the Ethics Committee of HCPA (protocol numbers 05-451, 06-237, and 06632012.4.0000.5334) and it was in accordance with the ethical standards established in the 1964 Declaration of Helsinki and its later amendments. Informed consent was obtained from all individual participants or legal representatives included in the study.

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12031_2018_1088_MOESM1_ESM.docx (17 kb)
ESM 1 (DOCX 17 kb)


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Authors and Affiliations

  • Lucas de Oliveira Pereira Ribeiro
    • 1
  • Pedro Vargas-Pinilla
    • 2
  • Djenifer B. Kappel
    • 2
  • Danae Longo
    • 2
  • Josiane Ranzan
    • 3
  • Michele Michelin Becker
    • 3
  • Rudimar dos Santos Riesgo
    • 3
  • Lavinia Schuler-Faccini
    • 2
  • Tatiana Roman
    • 2
  • Jaqueline Bohrer Schuch
    • 2
    • 4
    Email author
  1. 1.Department of Basic Health SciencesUniversidade de Ciências da Saúde de Porto AlegrePorto AlegreBrazil
  2. 2.Department of Genetics, Instituto de BiociênciasUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  3. 3.Child Neurology Unit, Hospital de Clínicas de Porto AlegreUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  4. 4.Laboratory of Immunosenescence, Graduate Program in Biomedical GerontologyPontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil

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