title: Genetic and expression analyses reveal elevated expression of syntaxin 1A ( STX1A) in high functioning autism.
abstract: Autism is a pervasive developmental disorder diagnosed in early childhood. Abnormalities of serotonergic neurotransmission have been reported in autism. Serotonin transporter (5-HTT), which modulates serotonin levels, is a major therapeutic target in autism. Therefore, factors that regulate 5-HTT expression might be implicated in autism. One candidate 5-HTT-regulatory protein is the presynaptic protein, syntaxin 1A (STX1A). We examined the association of STX1A with autism in a trio association study using DNA samples from 249 AGRE trios with autistic probands. Only male probands were selected, since autism is more prevalent among males. The probands of 102 trios had IQ>70, and were considered as high functioning autism (HFA). In transmission disequilibrium test (TDT) analysis, rs2293485 (p=0.034) and rs4717806 (p=0.033) showed nominal associations with HFA; modest haplotype association was also observed. The SNPs that showed associations were related to early developmental abnormalities (ADI-R_D). We further compared STX1A mRNA expression in the lymphocytes of drug-naive HFA patients (n=12) and age- and sex-matched controls (n=13). STX1A expression in the HFA group was significantly higher (p=0.001) than that of controls. Thus, we suggest a possible role of STX1A in the pathogenesis of HFA. During early childhood, there is a period of high brain serotonin synthesis that is disrupted in autistic children; STX1A might influence the serotonergic system during this stage of neurodevelopment, as implied by the association with ADI-R_D.
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan. nakamura@hama-med.ac.jp
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Ayyappan
authors.initials: A
authors.lastname: Anitha
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Tsujii
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama
authors.forename: Eiji
authors.initials: E
authors.lastname: Hattori
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Shiro
authors.initials: S
authors.lastname: Suda
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Takei
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Iwata
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Suzuki
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kawai
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Sekine
authors.forename: Kenji J
authors.initials: KJ
authors.lastname: Tsuchiya
authors.forename: Gen-Ichi
authors.initials: G
authors.lastname: Sugihara
authors.forename: Yasuomi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
mesh_terms: D001321:Autistic Disorder / Q000235:genetics* / Q000523:psychology*; D002648:Child; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050827:Syntaxin 1 / Q000235:genetics*; D020506:Untranslated Regions / Q000235:genetics; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D012333:RNA, Messenger; C494212:STX1A protein, human; D050827:Syntaxin 1; D020506:Untranslated Regions