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

Abstract

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.

Promoter Methylation and <b><i>BDNF</i></b> and <b><i>DAT1</i></b> Gene Expression Profiles in Patients with Drug Addiction

“…Studies of the DNA methylation profiles of the CpG island of the BDNF gene have shown that this gene could be useful as a biomarker of major depression [13,28]. The BDNF gene has been implicated as a susceptible locus for addiction to multiple drugs of abuse, such as alcohol.…”

“…This transporter is encoded by the SLC6A3 gene [13,31]. Recent studies have indicated that epigenetic mechanisms are directly involved in the molecular mechanisms that influence the genetic events that are involved in development as well as in the heritability of addiction to drugs of abuse [32,33].…”

“…These genes are important in brain function. BDNF, which is a component of the nerve growth factor family, has an important role in the development of the central nervous system and in synaptic plasticity [12,13]. Increased BDNF expression initiates changes in synaptic strength and neuronal signaling.…”

“…In the brain, BDNF protein is active at the connections between nerve cells (synapses) where cell-to-cell communication occurs. The BDNF gene is located in a region of chromosome 11p13 [13,15]. The DAT1 gene, which is also identified as SLC6A3 [16], is located on chromosome 5p15 and belongs to a family of Na/Cl-dependent transporters.…”

Saliva as a Blood Alternative for Genome-Wide DNA Methylation Profiling by Methylated DNA Immunoprecipitation (MeDIP) Sequencing

“…Next we examined genome-wide variation between the saliva and blood sample sets in genomic regions annotated to the following features: proximal promoters (2 kb upstream of RefSeq genes), RefSeq genes, coding sequences (CDS), LINEs (L1 and L2), SINEs (Alu), previously reported mental disorder-associated genes found by DNA methylation studies using peripheral tissue (BDNF, SLC6A4, CACNA1C, HTR1A, COMT, ST6GALNAC1, DRD2, and GAD1) [8,[67][68][69][70][71][72][73][74][75], and the above described DMWs. A box whisker plot of read counts in the grouped datasets at each genomic feature and a matching line graph for the individual datasets (normalized and summarized) showed a very similar profile with little variability and inter-individual difference, with DMWs as the natural exception ( Figure 4A,B).…”