title: Positive associations of polymorphisms in the metabotropic glutamate receptor type 3 gene (GRM3) with schizophrenia.
abstract: 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.
authors.affiliation: Division of Disease Genes, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Fujii
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shibata
authors.forename: Rumiko
authors.initials: R
authors.lastname: Kikuta
authors.forename: Chieko
authors.initials: C
authors.lastname: Makino
authors.forename: Ayako
authors.initials: A
authors.lastname: Tani
authors.forename: Naotsugu
authors.initials: N
authors.lastname: Hirata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shibata
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ninomiya
authors.forename: Nobutada
authors.initials: N
authors.lastname: Tashiro
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fukumaki
mesh_terms: 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*
chemical_list: D017931:DNA Primers; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; C104723:glutamate receptor ionotropic, AMPA 3