4.5 Article

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

Journal

INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
Volume 11, Issue 8, Pages 1073-1084

Publisher

OXFORD UNIV PRESS
DOI: 10.1017/S1461145708009036

Keywords

AGRE; high functioning autism; lymphocyte mRNA; serotonin transporter; syntaxin 1A

Funding

  1. Ministry of Health Labor and Welfare, Japan
  2. Ministry of Education, Culture, Sports, Science and Technology of Japan

Ask authors/readers for more resources

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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available