Positive associations of polymorphisms in the metabotropic glutamate receptor type 3 gene (GRM3) with schizophrenia.
OBJECTIVE
Glutamatergic dysfunction is one of the major hypotheses of schizophrenia pathophysiology. We have been conducting systematic studies on the association between glutamate receptors and schizophrenia. We focused on the metabotropic glutamate receptor type 3 gene (GRM3) as a candidate for schizophrenia susceptibility.


METHODS
We genotyped Japanese schizophrenics (n=100) and controls (n=100) for six single nucleotide polymorphisms (SNPs) located in the GRM3 region at intervals of approximately 50 kb. Statistical differences in genotype, allele and haplotype frequencies between cases and controls were evaluated by the chi2 test and Fisher's exact probability test at a significance level of 0.05. Haplotype frequencies were estimated by the EM algorithm.


RESULTS
A case-control association study identified a significant difference in allele frequency distribution of a SNP, rs1468412, between schizophrenics and controls (P=0.011). We also observed significant differences in haplotype frequencies estimated from SNP frequencies between schizophrenics and controls. The haplotype constructed from three SNPs, including rs1468412, showed a significant association with schizophrenia (P=8.30 x 10-4).


CONCLUSIONS
Our data indicate that at least one susceptibility locus for schizophrenia is situated within or very close to the GRM3 region in the Japanese patients.
Fujii
Yo
Y
Division of Disease Genes, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Japan.
Shibata
Hiroki
H
Kikuta
Rumiko
R
Makino
Chieko
C
Tani
Ayako
A
Hirata
Naotsugu
N
Shibata
Atsushi
A
Ninomiya
Hideaki
H
Tashiro
Nobutada
N
Fukumaki
Yasuyuki
Y
D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers; D005784:Gene Amplification; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D018091:Receptors, AMPA; D017470:Receptors, Glutamate / Q000235:genetics*; D012016:Reference Values; D012559:Schizophrenia / Q000235:genetics*
D017931:DNA Primers; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; C104723:glutamate receptor ionotropic, AMPA 3