title: Serotonin transporter gene polymorphisms and hyperserotonemia in autistic disorder.
abstract: Previous studies have provided conflicting evidence regarding the association of the serotonin transporter (5-HTT) gene with autism. Two polymorphisms have been identified in the human 5-HTT gene, a VNTR in intron 2 and a functional deletion/insertion in the promoter region (5-HTTLPR) with short and long variants. Positive associations of the 5-HTTLPR polymorphism with autism have been reported by two family-based studies, but one found preferential transmission of the short allele and the other of the long allele. Two subsequent studies failed to find evidence of transmission disequilibrium at the 5-HTTLPR locus. These conflicting results could be due to heterogeneity of clinical samples with regard to serotonin (5-HT) blood levels, which have been found to be elevated in some autistic subjects. Thus, we examined the association of the 5-HTTLPR and VNTR polymorphisms of the 5-HTT gene with autism, and we investigated the relationship between 5-HTT variants and whole-blood 5-HT. The transmission/disequilibrium test (TDT) revealed no linkage disequilibrium at either loci in a sample of 96 families comprising 43 trios and 53 sib pairs. Furthermore, no significant relationship between 5-HT blood levels and 5-HTT gene polymorphisms was found. Our results suggest that the 5-HTT gene is unlikely to play a major role as a susceptibility factor in autism.
authors.affiliation: INSERM U513, Faculté de Médecine, 94000 Créteil, France. betancur@im3.inserm.fr
authors.forename: C
authors.initials: C
authors.lastname: Betancur
authors.forename: M
authors.initials: M
authors.lastname: Corbex
authors.forename: C
authors.initials: C
authors.lastname: Spielewoy
authors.forename: A
authors.initials: A
authors.lastname: Philippe
authors.forename: J L
authors.initials: JL
authors.lastname: Laplanche
authors.forename: J M
authors.initials: JM
authors.lastname: Launay
authors.forename: C
authors.initials: C
authors.lastname: Gillberg
authors.forename: M C
authors.initials: MC
authors.lastname: Mouren-Siméoni
authors.forename: M
authors.initials: M
authors.lastname: Hamon
authors.forename: B
authors.initials: B
authors.lastname: Giros
authors.forename: M
authors.initials: M
authors.lastname: Nosten-Bertrand
authors.forename: M
authors.initials: M
authors.lastname: Leboyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001321:Autistic Disorder / Q000097:blood / Q000235:genetics*; D001792:Blood Platelets / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D026901:Membrane Transport Proteins; D018598:Minisatellite Repeats; D016254:Mutagenesis, Insertional; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D012307:Risk Factors; D017384:Sequence Deletion; D012701:Serotonin / Q000097:blood*; D050486:Serotonin Plasma Membrane Transport Proteins
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin