Evidence for an association with the serotonin transporter promoter region polymorphism and autism.
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.
Yirmiya
N
N
Hebrew University of Jerusalem, Jerusalem, Israel.
Pilowsky
T
T
Nemanov
L
L
Arbelle
S
S
Feinsilver
T
T
Fried
I
I
Ebstein
R P
RP
D000483:Alleles; D001321:Autistic Disorder / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics; D002648:Child; D004247:DNA / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; C493599:DRD4 protein, human; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D050638:Receptors, Dopamine D4; D004247:DNA; D002394:Catechol O-Methyltransferase