title: Evaluation of hypermethylation and expression pattern of GMR2, GMR5, GMR8, and GRIA3 in patients with schizophrenia.
abstract: Emerging evidence suggests a role of dysfunction of glutamatergic neurotransmission and its receptors in the pathophysiology of schizophrenia (SCZ). This study evaluated whether the promoter hypermethylation and RNA expression pattern of GMR2 (glutamate metabotropic receptor), GMR5, GMR8, and GRIA3 (glutamate receptor, ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) are associated with the risk of schizophrenia between schizophrenia patients and healthy controls.
  
  
  METHODS
  Methylation-specific polymerase chain reaction (MS-PCR) was used to estimate the promoter hypermethylation of GMR2, GMR5, GMR8, and GRIA3 genes on 81 isolated genomic DNA samples from the peripheral blood of individuals with schizophrenia and 71 healthy control subjects. In addition, real-time reverse transcription-PCR was used to estimate mRNA levels in 34 blood samples of healthy controls and cases.
  
  
  RESULTS
  The methylation of GRM2 and GRM5 greatly decreased the risk of schizophrenia in comparison to the reference unmethylated pattern [OR=0.38, 95% CI; 0.144-1.035, p=0.05; OR=0.06, 95% CI; 0.007-0.54.10, p=0.01], respectively. The methylation of GRIA3 highly increased the risk of schizophrenia, but non-significant (OR=2.3, 95% CI; 0.51-10.42). The outcomes of the expression analysis revealed a statistically significant difference between the cases (n=17) and healthy controls (n=17) regarding the relative gene expression of GRM2, GRM5, and GRIA3 (p=0.0001).
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first evidence showing that the promoter methylation of the GMR2 and GMR5 genes greatly decreased the risk of schizophrenia, and the expression level of the GRM2, GRM5, and GRIA3 genes increased significantly in patients in comparison to healthy controls. These outcomes suggest that there is a need for more attention to be paid to the effect of epigenetic variations in the development of SCZ in further investigations.
authors.affiliation: Department of Biology, University of Sistan and Baluchestan, Zahedan, Iran. dor_kordi@yahoo.com
authors.forename: Dor Mohammad
authors.initials: DM
authors.lastname: Kordi-Tamandani
authors.forename: Nahid
authors.initials: N
authors.lastname: Dahmardeh
authors.forename: Adam
authors.initials: A
authors.lastname: Torkamanzehi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D064529:Receptor, Metabotropic Glutamate 5; D018091:Receptors, AMPA / Q000235:genetics*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
chemical_list: C578935:GRM5 protein, human; D064529:Receptor, Metabotropic Glutamate 5; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; C104723:glutamate receptor ionotropic, AMPA 3; C108822:metabotropic glutamate receptor 2; C111435:metabotropic glutamate receptor 8