Association of glutathione s-transferase gene methylation with risk of schizophrenia in an Iranian population.

BACKGROUND/AIM: It has been believed that epigenetic changes play a critical role in schizophrenia through improper interaction between genome and environmental risk factors. The aim of this case-control study was to investigate the association of the promoter hypermethylation status of glutathione S-transferase T1 (GSTT1) and glutathione S-transferase P1 (GSTP1) genes with the risk of schizophrenia. MATERIALS AND METHODS: Methylation-specific PCR was used to estimate DNA methylation in the blood of 80 patients with schizophrenia and 71 healthy controls. RESULTS: Promoter hypermethylation analysis of GSTT and GSTP indicated a significant difference between individuals with methylated and unmethylated status [odds ratio (OR) = 0.339, 95% confidence interval (95% CI) = 0.14-0.8, p = 0.012 and OR = 0.308, 95% CI = 0.135-0.7, p = 0.005, respectively]. CONCLUSION: The present study supports the hypothesis that impairment in the promoter region of GSTT and GSTP genes by hypermethylation may increase the risk of schizophrenia.

Analysis of association between dopamine receptor genes' methylation and their expression profile with the risk of schizophrenia.

OBJECTIVE: Schizophrenia (SCZ) is a type of psychotic disorder that affects ~1% of the population. Dopamine is one of the major neurotransmitters in the brain and its receptors are associated with a number of psychotic disorders, including SCZ. The aims of the present study were to analyze methylation and the expression profile of dopamine receptor DRD1, DRD2, DRD4, and DRD5 genes in patients with SCZ. MATERIALS AND METHODS: Promoter methylation of DRD1, DRD2, DRD4, and DRD5 genes was assayed by a methylation-specific PCR in blood samples obtained from 80 SCZ cases and 71 healthy controls. Also, we investigated DRD1, DRD2, DRD4, and DRD5 mRNA levels using real-time reverse transcription PCR in 34 blood samples of healthy controls and cases. RESULTS: Promoter methylation of DRD4, DRD5, and DRD2 genes was statistically different in cases compared with healthy controls. The mRNA expression level results also showed statistically significant differences (P<0.0001) between cases and healthy controls for the DRD2, DRD4, and DRD5 genes, but not for DRD1. CONCLUSION: Analyses of DRD genes' methylation have highlighted the fact that the DRD gene network, overall, is actively involved in the increased risk of SCZ.

DNA methylation and expression profiles of the brain-derived neurotrophic factor (BDNF) and dopamine transporter (DAT1) genes in patients with schizophrenia.

Methylation and expression profile of CpG islands were examined in the promoters of the brain-derived neurotrophic factor (BDNF) and dopamine transporter (DAT1) genes. These are well known to be involved in the pathophysiology of psychiatric disorders such as schizophrenia. Genomic DNA was extracted from peripheral blood of 80 patients with schizophrenia and 71 healthy controls. Methylation pattern was studied by Methylation-Specific PCR. RNA expression analysis was done on extracted RNA from blood samples from patients suffering from schizophrenia (n = 17) and healthy controls (n = 17). Frequency of the BDNF gene methylation was highlighted as a statistically significant relationship between cases and controls regarding decreased risk of disease in comparison to unmethylated patterns (OR = 0.24; 95 % CI = 1.11-0.50; P = 0.00007). For the DAT1 gene, this relationship was insignificant in 61 cases (76.25 %) and 52 controls (73.23 %) (OR = 1.17; 95 % CI = 0.53-2.61). Estimates of relative gene expression revealed a statistically significant association of the BDNF gene between schizophrenic patients and healthy controls (Mean ± SD: 13.3920 ± 15.19 and 0.437 ± 0.328, P = 0.0001) respectively; however, it was not significant for the DAT1 gene. This first hand evidence, regarding BDNF and DAT1 gene methylation and their expression profile with risk of schizophrenia, indicated a significant function for the BDNF gene in the development of schizophrenia. However, further populations with large sample sizes need to be studied to verify the exact role of BDNF in mental disorders such as schizophrenia.

Analysis of glutathione S-transferase genes polymorphisms and the risk of schizophrenia in a sample of Iranian population.

Glutathione S-transferases (GSTs) are major intracellular antioxidants, which, impaired in their function, are involved in the progress of schizophrenia (SCZ). The aim of this case-control study was to investigate the association between the polymorphism of glutathione S-transferases M1 (GSTM1), T1 (GSTT1), the glutathione S-transferase P1 gene (GSTP1) and SCZ. We isolated genomic DNA from peripheral blood of 93 individuals with SCZ and 99 healthy control subjects' genotypes analyzing them for GSTM1, GSTT1 and GSTP1 using polymerase chain reaction. The analysis of the gene-gene interaction between GSTs indicated that the magnitude of the association was greater for the combined AG/GSTT1 & GSTM1 genotypes (OR = 2.51; 95% CI: 1.13-5.63, P = 0.02). The AG and combined AG + GG genotypes of GSTP1 increased the risk of SCZ (OR = 1.83; 95% CI: 0.94-3.75 and OR = 1.71; 95% CI: 0.92-3.19, respectively). The genotypes of GSTT/NULL, NULL/GSTM and NULL/NULL increased the risk of SCZ (OR = 2.05; 95% CI: 0.9-4.74; OR = 2.0; 95% CI: 1.68-2.31; and OR = 1.8; 95% CI: 0.57-2.46, respectively). The present study supports previous data that suggest that impairment in the function of GSTs genes may increase the risk of SCZ.