Glutamate AMPA receptor subunit 1 gene (GRIA1) and DSM-IV-TR schizophrenia: a pilot case-control association study in an Italian sample

Glutamatergic dysfunction is one of the major
hypotheses for the pathogenesis of schizophrenia.
The GRIA1 gene encodes for one (GluR1) of the
four (GluR1–4) ionotropic AMPA receptor subunits.
GRIA1 is a good candidate gene for susceptibility
to schizophrenia since it maps in 5q33, a
region where the presence of susceptibility loci
has been suggested by independent genome-wide
scans and because its expression has been found
to be decreased in the brain of someschizophrenia
patients. We present data from a case-control
association study on the Italian population with
eight polymorphisms spanning the whole GRIA1
gene. Single-locus analysis revealed a significantly
different allele distribution in cases and
in controls of two SNPs (rs707176, 0.41 vs. 0.31,
P¼0.009; rs2963944, 0.41 vs. 0.30, P¼0.007), and
one microsatellite (rs10631988, allele 9: 0.40 vs.
0.29, P¼0.004). Haplotype analysis showed an
increased frequency of a specific haplotype for
these markers (C09CC, 0.39 vs. 0.28, P¼0.009).
Therefore our data indicate that GRIA1 may be
involved in susceptibility to DSM-IV-TR schizophrenia.