MISC

2008年12月

Genetic and expression analyses reveal elevated expression of syntaxin 1A (STX1A) in high functioning autism

INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
  • Kazuhiko Nakamura
  • Ayyappan Anitha
  • Kazuo Yamada
  • Masatsugu Tsujii
  • Yoshimi Iwayama
  • Eiji Hattori
  • Tomoko Toyota
  • Shiro Suda
  • Noriyoshi Takei
  • Yasuhide Iwata
  • Katsuaki Suzuki
  • Hideo Matsuzaki
  • Masayoshi Kawai
  • Yoshimoto Sekine
  • Kenji J. Tsuchiya
  • Gen-ichi Sugihara
  • Yasuomi Ouchi
  • Toshiro Sugiyama
  • Takeo Yoshikawa
  • Norio Mori
  • 全て表示

11
8
開始ページ
1073
終了ページ
1084
記述言語
英語
掲載種別
DOI
10.1017/S1461145708009036
出版者・発行元
CAMBRIDGE UNIV PRESS

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 (STMA). 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 neuro-development, as implied by the association with ADI-R_D.

リンク情報
DOI
https://doi.org/10.1017/S1461145708009036
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000261112100005&DestApp=WOS_CPL
ID情報
  • DOI : 10.1017/S1461145708009036
  • ISSN : 1461-1457
  • eISSN : 1469-5111
  • Web of Science ID : WOS:000261112100005

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