[Evidence for Association and Epistasis Between the Genetic Markers SLC6A4 and HTR2A in Autism Etiology]

Biomedica. Oct-Dec 2012;32(4):585-601. doi: 10.1590/S0120-41572012000400014.
[Article in Spanish]


Introduction: Autism spectrum disorders are severe neurodevelopmental disorders with a strong genetic component. The potential role of the serotoninergic system in the development of autistic disorder has been based on the observation of hyperserotoninemia in autistic subjects and the results of drug treatment studies. Multiple molecules involved in serotonin metabolism and neurotransmission have been studied; however, replication studies have been inconsistent. This may be partially related to the marked genetic heterogeneity of autism in different populations.

Objectives: The relationship between autism and single nucleotide polymorphisms of SLC6A4, HTR2A and ITGB3 genes was evaluated in an urban population of northwestern Colombia.

Materials and methods: In Antioquia, Colombia, 42 families with history of autism were screened for 10 SNPs in SLC6A4, HTR2A and ITGB3 genes and evaluated for associations with the transmission disequilibrium test. The interactions among these genes and autism was assessed with multidimensional reduction methods.

Results: A significant main effect was seen among the SLC6A4 gene variants rs4583306 (OR=2.6, p=0.004) and rs2066713 (OR=2.2, p=0.03). No main effect of the ITGB3 or HTR2A variants was found, however, in the interaction effects, the SLC6A4 and HTR2A genes demonstrated significant evidence of association with autism (p<0.001).

Conclusion: Significant association of markers were discovered within the SLC6A4 gene and the combination of SLC6A4 and HTR2A (S-A) genes to autism. These results were consistent with previous studies conducted in other populations and provide further evidence for the implication of the serotoninergic system in the etiology of autistic disorders.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child Development Disorders, Pervasive / epidemiology
  • Child Development Disorders, Pervasive / genetics*
  • Child, Preschool
  • Colombia / epidemiology
  • Epistasis, Genetic*
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genotype
  • Humans
  • Integrin beta3 / genetics*
  • Linkage Disequilibrium
  • Male
  • Polymorphism, Single Nucleotide*
  • Receptor, Serotonin, 5-HT2A / genetics*
  • Serotonin / physiology
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Symptom Assessment


  • ITGB3 protein, human
  • Integrin beta3
  • Receptor, Serotonin, 5-HT2A
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin