Friday, May 16, 2008: 2:00 PM
Bourgogne (Novotel London West)
K. Nakamura
,
Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan
A. Ayyappan
,
Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan
K. Yamada
,
Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan
S. Suda
,
Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan
M. Tsujii
,
Faculty of Sociology, Chukyo University, Aichi, Japan
Y. Iwayama
,
Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan
T. Miyachi
,
The Osaka-Hamamatsu Joint Reserach Center for Child Mental Development, Hamamatsu University School of Medicine, Shizuoka, Japan
H. Matsuzaki
,
The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Graduate School of Medicine, Osaka University, Osaka, Japan
K. J. Tsuchiya
,
The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan
T. Sugiyama
,
Aichi Chilren's Health and Medical Center, Aichi, Japan
N. Takei
,
The Osaka-Hamamatsu Joint Reserach Center for Child Mental Development, Hamamatsu University School of Medicine, Shizuoka, Japan
T. Yoshikawa
,
Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan
N. Mori
,
Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan
Background:
autism is a pervasive developmental disorder diagnosed in early childhood. Abnormalities of serotonergic neurotransmission have been reported in autism. Serotonin transporter (SERT) modulates serotonin levels, and is a major therapeutic target in autism. Factors that regulate SERT expression might be implicated in the pathophysiology of autism.Objectives: SERT expression in Drosophila is reported to be regulated by the roundabout axon guidance molecule, robo; ROBO proteins (ROBO1, 2, 3, and 4) play a vital role in mammalian neurodevelopment also. We examined the associations of ROBO genes with autism, in a trios association study. Further, we compared the mRNA expressions of ROBO genes in the autistic patients and control subjects.
Methods: DNA samples from trio families recruited to the AGRE were used for this study; 252 trio families, with male offspring scored for autism, were selected. Genotypes were determined in ABI PRISM 7900HT Sequence Detection System. One-way analysis of variance was used to examine the variability in the distribution of ADI-R phenotypic data. We further compared the mRNA expressions of ROBO genes in the lymphocytes of 19 drug-naïve autistic patients and 20 matched controls.
Results: four SNPs of ROBO3 (rs3923890, p=0.023; rs7925879, p=0.017; rs4606490, p=0.033 and rs3802905, p=0.049) and a single SNP of ROBO4 (rs6590109, p=0.009) showed significant associations with autism, by transmission disequilibrium test; the A/A genotype of rs3923890 showed lower ADI-R_A scores, which reflect social interaction. Significant haplotype associations were also observed for ROBO3 and ROBO4. Expressions of ROBO1 (p=0.018) and ROBO2 (p=0.023) were significantly reduced in the autistic group; the possibility of using the altered expressions of ROBO as peripheral markers for autism, may be explored.
Conclusions: we suggest a possible role of ROBO in the pathogenesis of autism. Abnormalities of ROBO may lead to autism either by interfering with serotonergic system, or by disrupting neurodevelopment.
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