Evidence for an association with the serotonin transporter promoter region polymorphism and autism

Am J Med Genet. 2001 May 8;105(4):381-6. doi: 10.1002/ajmg.1365.


We have examined three functional polymorphisms, serotonin transporter promoter region polymorphism (5-HTTLPR), dopamine D4 exon III repeat region (DRD4), and catechol-O-methyltransferase (COMT), in a small family-based design toward identifying candidate genes that confer risk for autism. A significant excess of the long/long 5-HTTLPR genotype was observed (likelihood ratio = 7.18; P = 0.027; 2 df; n = 33 families) as well as preferential transmission of the long allele of the 5-HTTLPR (TDT chi-square = 5.44; P<0.025; 1 df). No association was observed between the COMT and DRD4 polymorphisms and autism in this sample. Some previous studies have observed linkage between autism and the 5-HTTLPR polymorphism and the current results are similar to those first reported by Klauck et al. [1997: Hum Genet 100:224-229; 1997: Hum Mol Genet 6:2233-2238]. Additionally, elevated serotonin levels have been consistently found in 30%-50% of autistic patients and may represent a marker for familial autism. Hyperserotonemia in autism appears to be due to enhanced 5-HT uptake, as free 5-HT levels are normal and the current report of an excess of the long/long 5-HTTLPR genotype in autism could provide a partial molecular explanation for high platelet serotonin content in autism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alleles
  • Autistic Disorder / genetics*
  • Autistic Disorder / pathology
  • Carrier Proteins / genetics*
  • Catechol O-Methyltransferase / genetics
  • Child
  • DNA / genetics
  • Gene Frequency
  • Genotype
  • Humans
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Polymorphism, Genetic
  • Promoter Regions, Genetic / genetics*
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D4
  • Serotonin Plasma Membrane Transport Proteins


  • Carrier Proteins
  • DRD4 protein, human
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Receptors, Dopamine D2
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Receptors, Dopamine D4
  • DNA
  • Catechol O-Methyltransferase