Evidence for an association with the serotonin transporter promoter regionpolymorphism and autism

We have examined three functional polymorphisms, serotonin transporter prom oter region polymorphism (5-HTTLPR), dopamine D4 exon III repeat region (DR D4), surd catechol-O-methyltransferase (COMT), in a small family-based desi gn toward identifying candidate genes that confer risk for autism. A signif icant excess of the long/long 5-HTTLPR genotype was observed (likelihood ra tio = 7.18; P = 0.027; 2 df; n = 33 families) as well as preferential trans mission of the long allele of the 5-HTTLPR (TDT chi-square = 5.44; P < 0.02 5; 1 df). No association was observed between the COMT and DRD4 polymorphis ms and autism in this sample. Some previous studies have observed linkage b etween autism and the 5-HTTLPR polymorphism and the current results are sim ilar 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 repres ent 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 pro vide a partial molecular explanation for high platelet serotonin content in autism. (C) 2001Wiley-Liss,Inc.