title: Lack of association between serotonin transporter gene promoter variants and autistic disorder in two ethnically distinct samples.
abstract: Family-based studies performed to date provide conflicting evidence of linkage/association between autistic disorder and either the "short" [Cook et al., 1997: Mol Psychiatry 2:247-250] or the "long" [Klauck et al., 1997: Hum Mol Genet 6:2233-2238] allele of a polymorphic repeat located in the serotonin transporter (5-HTT) gene promoter region, affecting 5-HTT gene expression [Lesch et al., 1996: Science 274:1527-1531]. The present study was designed to assess linkage and linkage disequilibrium in two new ethnically distinct samples of families with primary autistic probands. The 5-HTT promoter repeat was genotyped in 54 singleton families collected in Italy and in 32 singleton and 5 multiplex families collected in the U.S.A., yielding a total sample of 98 trios. Linkage/association between 5-HTT gene promoter alleles and autistic disorder was assessed using the transmission/disequilibrium test (TDT) and the haplotype-based haplotype relative risk (HHRR). Both the Italian and the American samples, either singly or combined, displayed no evidence of linkage/association between 5-HTT gene promoter alleles and autistic disorder. Our findings do not support prominent contributions of 5-HTT gene variants to the pathogenesis of idiopathic infantile autism. Heterogeneity in pathogenetic mechanisms underlying the disease may require that linkage/association studies be targeted toward patient subgroups isolated on the basis of specific biochemical markers, such as serotonin (5-HT) blood levels. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:123-127, 2000.
authors.affiliation: Laboratory of Neuroscience, Department of Physiology and Neuroscience, Libera Universita' "Campus Bio-Medico," Rome, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Persico
authors.forename: R
authors.initials: R
authors.lastname: Militerni
authors.forename: C
authors.initials: C
authors.lastname: Bravaccio
authors.forename: C
authors.initials: C
authors.lastname: Schneider
authors.forename: R
authors.initials: R
authors.lastname: Melmed
authors.forename: M
authors.initials: M
authors.lastname: Conciatori
authors.forename: V
authors.initials: V
authors.lastname: Damiani
authors.forename: A
authors.initials: A
authors.lastname: Baldi
authors.forename: F
authors.initials: F
authors.lastname: Keller
mesh_terms: D000293:Adolescent; D001321:Autistic Disorder / Q000208:ethnology / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D005260:Female; D006239:Haplotypes; D006801:Humans; D007558:Italy / Q000208:ethnology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011401:Promoter Regions, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins; D014481:United States / Q000208:ethnology
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins