Is the G72/G30 locus associated with schizophrenia? Single nucleotide polymorphisms, haplotypes, and gene expression analysis

Michael Korostishevsky, Miryam Kaganovich, Alina Cholostoy, Maya Ashkenazi, Yael Ratner, Dvir Dahary, Jeanne Bernstein, Ullrike Bening-Abu-Shach, Edna Ben-Asher, Doron Lancet, Michael Ritsner, Ruth Navon

Research output: Contribution to journalArticlepeer-review

Abstract

Background The genes G72/G30 were recently implicated in schizophrenia in both Canadian and Russian populations. We hypothesized that 1) polymorphic changes in this gene region might be associated with schizophrenia in the Ashkenazi Jewish population and that 2) changes in G72/G30 gene expression might be expected in schizophrenic patients compared with control subjects. Methods Eleven single nucleotide polymorphisms (SNPs) encompassing the G72/G30 genes were typed in the genomic deoxyribonucleic acid (DNA) from 60 schizophrenic patients and 130 matched control subjects of Ashkenazi ethnic origin. Case-control comparisons were based on linkage disequilibrium (LD) and haplotype frequency estimations. Gene expression analysis of G72 and G30 was performed on 88 postmortem dorsolateral prefrontal cortex samples. Results Linkage disequilibrium analysis revealed two main SNP blocks. Haplotype analysis on block II, containing three SNPs external to the genes, demonstrated an association with schizophrenia. Gene expression analysis exhibited correlations between expression levels of the G72 and G30 genes, as well as a tendency toward overexpression of the G72 gene in schizophrenic brain samples of 44 schizophrenic patients compared with 44 control subjects. Conclusions It is likely that the G72/G30 region is involved in susceptibility to schizophrenia in the Ashkenazi population. The elevation in expression of the G72 gene coincides with the glutamatergic theory of schizophrenia.

Original languageEnglish
Pages (from-to)169-176
Number of pages8
JournalBiological Psychiatry
Volume56
Issue number3
DOIs
StatePublished - 1 Aug 2004

Keywords

  • Ashkenazi Jews
  • Schizophrenia
  • dorsolateral prefrontal cortex
  • linkage disequilibrium
  • real-time polymerase chain reaction
  • susceptibility genes

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