Abstract
Background
Synapsin III plays a role in neuronal plasticity and maps to chromosome 22q12-13,
a region suggested to be linked to schizophrenia. To determine if synapsin III plays
a role in this disease, we searched for polymorphisms in this gene in patients with
schizophrenia and controls.
Methods
The synapsin III gene was initially sequenced from 10 individuals with schizophrenia
to identify polymorphisms. Association analysis was then performed using 118 individuals
with schizophrenia and 330 population controls. Synapsin III expression was studied
by immunoblot analyses, and phosphorylation sites were mapped by sequencing trypsin-digested
synapsin III fragments phosphorylated with phosphorus-32.
Results
A rare, missense polymorphism, S470N, was identified in the synapsin III gene and
appeared more frequently in individuals with schizophrenia than in controls (p = .0048). The site affected by the polymorphism, Ser470, was determined to be a substrate
for mitogen-activated protein kinase, a downstream effector of neurotrophin action.
Phosphorylation at Ser470 was increased during neonatal development and in response
to neurotrophin-3 in cultured hippocampal neurons.
Conclusions
Our observations suggest an association of a rare polymorphism in synapsin III with
schizophrenia, but further studies will be required to clarify its role in this disease.
Keywords
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Article info
Publication history
Accepted:
July 24,
2003
Received in revised form:
July 9,
2003
Received:
March 26,
2003
Identification
Copyright
© 2004 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
