DNA methylation at the putative promoter region of the human dopamine D2 receptor gene

Abstract

DNA methylation was investigated in the putative promoter region of the human dopamine D2 receptor gene (DRD2). Twenty-two DNA samples from two types of cells differentially expressing D2 receptors, striatum and lymphocytes, were subjected to bisulphite modification-based mapping of methylated cytosines. In the tested region, the DNA from lymphocytes exhibited a significantly higher degree of methylation than that from striata. In addition, a significantly higher proportion of methylated to unmethylated cytosines was detected in DRD2 from the right than the left striatum, and a trend towards a greater degree of methylation was detected in older than in younger individuals. These DRD2 methylation findings are consistent with dopamine D2 receptor binding data from the literature which support the idea that DNA methylation plays a role in regulation of DRD2 expression.

The myelin-pathogenesis puzzle in schizophrenia: a literature review

“…49 Potential causes of pathological DNA hypermethylation which have been indicated as risk factors for schizophrenia include some environmental insults, such as ephemeral ischemia with a consequent increase of DNA methylation, nitric oxide, which has neurodegenerative effects in focal ischemia, intrauterine environmental conditions and maternal malnutrition, alcohol abuse during pregnancy, birth and obstetric complications, as well as exposure to drugs and chemicals, hormonal status (for example, estradiol, estrogen, steroid hormones) and viral infections. 49,165,168 Besides the above data, 49,158,161,162 reported downregulation of histone deacetylase 3 in the temporal cortex of patients with schizophrenia 102 and epigenetic variations in the genes for serotonin 2A (HTR2A) and the dopamine D3 (DRD3) and D2 (DRD2) receptors 163,169 provide further supplementary evidence for the contribution of epigenetic misregulation in schizophrenia. Interestingly, the finding of different degrees of methylation of the promoter area of DRD2 between the right and left striatum 169 introduces the possibility that the epigenetic mechanisms play a role in brain hemisphere laterality 165 and provides a new interpretation of the reported anomalous cerebral asymmetry in affected individuals.…”

“…49,165,168 Besides the above data, 49,158,161,162 reported downregulation of histone deacetylase 3 in the temporal cortex of patients with schizophrenia 102 and epigenetic variations in the genes for serotonin 2A (HTR2A) and the dopamine D3 (DRD3) and D2 (DRD2) receptors 163,169 provide further supplementary evidence for the contribution of epigenetic misregulation in schizophrenia. Interestingly, the finding of different degrees of methylation of the promoter area of DRD2 between the right and left striatum 169 introduces the possibility that the epigenetic mechanisms play a role in brain hemisphere laterality 165 and provides a new interpretation of the reported anomalous cerebral asymmetry in affected individuals. The epigenetic hypothesis provides a new perspective on the etiopathogenesis of schizophrenia and on the various non-Mendelian characteristics of the disease, such as the presence of clinically indistinguishable sporadic and familial cases, phenotypic variance, discordance of monozygotic twins, coincidence of peaks of disease onset with major endocrine rearrangements and the fluctuating course of disease severity.…”

Resistance to dopamine agonists in prolactinoma is correlated with reduction of dopamine D2 receptor long isoform mRNA levels

“…Rapid DNA Bisulphite Modification kit (Human Genetic Signatures Pty Ltd, North Ryde, Australia) according to the manufacturer's instructions. The promoter region of the DRD2 gene, which extends from K239 to C146 (the first nucleotide of exon 1 assigned as position C1), is a CG rich containing region (C15 to C44) that has been reported to be differentially methylated between striatum and lymphocytes (17). We set two forward primers from K239 to K219 (5 0 -TATTTTGGGTGTGG-GTGGGAG-3 0 ) and from K124 to K104 (5 0…”

Epigenetic aberration of the human REELIN gene in psychiatric disorders

“…[4][5][6][7][8] To better understand the implications of DNA methylation in disease susceptibility, it is necessary to examine both the qualitative and quantitative status of DNA methylation within the genome.…”