Serotonin transporter (5-HTT) gene variants associated with autism?

Hum Mol Genet. 1997 Dec;6(13):2233-8. doi: 10.1093/hmg/6.13.2233.


An association study was performed to elucidate the role of the serotonin transporter (5-HTT) gene as a susceptibility factor for autism as treatment of patients with antidepressant drugs which selectively target 5-HTT reduced autistic or concomitant symptoms, such as repetitive behavior and aggression, and ameliorate language use. Using the transmission/disequilibrium test (TDT) an analysis was done for a common polymorphism in the upstream regulatory region (5-HTTLPR), a VNTR in intron 2 of the gene and a haplotype of both loci in 52 trios fulfilling stringent criteria for autism and an extended group of 65 trios including patients showing no language delay in their first 3 years of life. A higher frequency and preferential transmission of the long allele of the 5-HTTLPR was observed, but the TDT gave a statistically significant value ( P = 0. 032) only for the extended patient group. This result is in contrast to a recent study by a US group presenting preliminary evidence for preferential transmission of the short allele of 5-HTTLPR in 86 trios. Both studies failed to reveal significant linkage disequilibrium between the VNTR in intron 2 of the gene and autism. In our study haplotype analysis of the 5-HTTLPR and the VNTR in intron 2 supplied evidence for an association of 5-HTT and autism in the stringent ( P = 0.069) and extended patient group ( P = 0.049). Overall, we were not able to replicate the findings of the first study on 5-HTT and autism and instead observed a tendency for association of the opposite genetic variant of the gene with the disorder. The implications for genetic variants of the serotonin transporter in the etiology of autism and possible subgroups of patients, therefore, needs clarification in further studies with other and larger patient samples.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Autistic Disorder / classification
  • Autistic Disorder / ethnology
  • Autistic Disorder / genetics*
  • Autistic Disorder / psychology
  • Carrier Proteins / genetics*
  • Child
  • Child, Preschool
  • Disease Susceptibility
  • Female
  • Germany / epidemiology
  • Haplotypes / genetics
  • Humans
  • Introns / genetics
  • Language Development
  • Linkage Disequilibrium
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins*
  • Minisatellite Repeats*
  • Nerve Tissue Proteins / genetics*
  • Polymorphism, Genetic*
  • Reproducibility of Results
  • Serotonin Plasma Membrane Transport Proteins
  • United States / epidemiology


  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins