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

Abstract

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.

• Authors: N Yirmiya, T Pilowsky, L Nemanov, S Arbelle, T Feinsilver, I Fried, R P Ebstein
• Journal: American journal of medical genetics (Am J Med Genet) Vol. 105 Issue 4 Pg. 381-6 (May 08 2001) ISSN: 0148-7299 [Print] United States
• PMID: 11378854 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright 2001 Wiley-Liss, Inc.

Chemical References

• 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

Topics

• Alleles
• Autistic Disorder (genetics, 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