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.
Department of Biology, University of Sistan and Baluchestan, P.O. Box 98155-987, Zahedan, Iran. dor_kordi@yahoo.com
Dor Mohammad
DM
Kordi-Tamandani
Roya
R
Sahranavard
Adam
A
Torkamanzehi
D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D019175:DNA Methylation / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D012559:Schizophrenia / Q000235:genetics*; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; C579455:BDNF protein, human