| 1 | Schizophr. Res. 2008 Jan 98: 111-7 |
|---|---|
| PMID | 17961987 |
| Title | Histone deactylase 1 expression is increased in the prefrontal cortex of schizophrenia subjects: analysis of the National Brain Databank microarray collection. |
| Abstract | Histone deactylase enzymes are responsible for the deacetylation of histone tails, and consequently influence gene regulation through their ability to modify chromatin structure surrounding promoter regions. We analyzed the microarray collection of the National Brain Databank to investigate differential expression of these enzymes in the prefrontal cortices of control, schizophrenia and bipolar subjects. HDAC1 expression levels were significantly higher in schizophrenia versus normal subjects. The mRNA expression level of an epigenetically regulated schizophrenia candidate gene GAD67 was strongly and negatively correlated with the mRNA expression levels of HDAC1, HDAC3 and HDAC4 levels. These findings provide additional support for the proposal that epigenetic factors are operative in the brain pathology of patients with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Psychiatry Res 2010 Jul 178: 266-9 |
| PMID | 20471694 |
| Title | Association of histone deacetylase genes with schizophrenia in Korean population. |
| Abstract | Histone deacetylases (HDACs) are pivotal enzymes in the epigenetic modification or regulatory mechanisms of gene transcription. Based on previous assertions that the pathophysiology of schizophrenia is associated with epigenetics, we hypothesized that polymorphisms of HDAC genes might be related to schizophrenia. We recruited 278 patients with schizophrenia and 234 normal controls from a Korean population. Clinical information of the group with schizophrenia was obtained from medical records, the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the Operational Criteria Checklist (OPCRIT). Three single-nucleotide polymorphisms (SNPs) in HDAC genes were selected, including rs2530223 of HDAC3, rs1063639 of HDAC4, and rs1555048 of HDAC10. For the analysis of genetic data, SNPStats, SNPAnalyzer, and Helixtree programs were used. In the present study, rs1063639 of the HDAC4 gene showed associations with schizophrenia in the codominant and dominant models. In the analysis of clinical phenotypes, smoking status was associated with rs2530223 of HDAC3 in the codominant and recessive models. The results suggest that HDAC3 and HDAC4 genes might play a role in the pathophysiology of schizophrenia in a Korean population. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Asia Pac Psychiatry 2013 Mar 5: 11-6 |
| PMID | 23857786 |
| Title | Associations of histone deacetylase-2 and histone deacetylase-3 genes with schizophrenia in a Chinese population. |
| Abstract | To explore the association between histone deacetylase-2 (HDAC2) and histone deacetylase-3 (HDAC3) gene polymorphisms and schizophrenia. A total of 208 family trios consisting of fathers, mothers and affected offspring with schizophrenia were recruited as our subjects. Four tag SNPs on HDAC2 (rs10499080, rs6568819, rs2499618 and rs13204445) and two tag SNPs on HDAC3 (rs11741808, rs2530223) genes were selected. The Mass ARRAY Assay Design software (Sequenom) was used to design amplification and allele specific extension primers. The Hardy-Weinberg equilibrium (HWE) for genotypic distributions was tested using the chi-square goodness-of-fit test. Allelic association for a single tag SNP was analyzed by using family-based association tests including the haplotype-based haplotype relative risk (HHRR) test and the transmission disequilibrium test (TDT). The genotypic distributions of HDAC2 SNPs rs6568819, rs2499618 and rs13204445 and HDAC3 SNPs rs11741808 and rs2530223 were all in Hardy-Weinberg equilibrium (P > 0.05). HHRR analysis revealed no associations between the SNPs and schizophrenia (P > 0.05). In addition, the TDT did not show any significant associations between HDAC2 and HDAC3 SNPs and schizophrenia (P > 0.05). HDAC2 and HDAC3 might not be associated with schizophrenia in the Chinese population. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Schizophr. Res. 2014 Dec 160: 97-103 |
| PMID | 25445625 |
| Title | Family-based association study of common variants, rare mutation study and epistatic interaction detection in HDAC genes in schizophrenia. |
| Abstract | Histone deacetylases (HDACs) are key enzymes of histone acetylation, and abnormalities in histone modifications and in the level of HDAC proteins have been reported in schizophrenia. The objective of the present study was to systematically test the HDAC genes for its association with schizophrenia. A family-based genetic association study (951 Caucasian subjects in 313 nuclear families) using 601 tag-single nucleotide polymorphisms in HDAC genes was conducted followed by a replication study of top-ranked markers in a sample of 1427 Caucasian subjects from 241 multiplex families and 176 trios. Epistasis interaction was tested by using the pedigree-based generalized multifactor dimensionality reduction (GMDR). Furthermore, we analyzed exome sequencing data of 1134 subjects for detection of rare mutations in HDAC genomic regions. In the exploratory study, ten markers were in significant association with schizophrenia (P<0.01). One maker rs14251 (HDAC3) was replicated (P=0.04) and remained significant in the whole sample (P=0.004). GMDR identified that a significant three-locus interaction model was detected involving rs17265596 (HDAC9), rs7290710 (HDAC10) and rs7634112 (HDAC11) with a good testing accuracy (0.58). No rare mutations were found associated with schizophrenia. This first exploratory systematic study of the HDAC genes provides consistent support for the involvement of the HDAC3 gene in the etiology of schizophrenia. A statistical epistatic interaction between HDAC9, HDAC10, and HDAC11 was detected and seems biologically plausible. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Neurosci. Lett. 2014 Oct 582: 120-4 |
| PMID | 25196196 |
| Title | Dysbindin-1, a schizophrenia-related protein, interacts with HDAC3. |
| Abstract | DTNBP1 is a key candidate gene associated with schizophrenia. The expression of its protein product, dysbindin-1, is altered in the brains of schizophrenic patients; however, the physiological functions of dysbindin-1 in the central nervous system are unclear. Several studies have shown that both dysbindin-1 and histone deacetylase 3 (HDAC3) can be phosphorylated by the DNA-dependent protein kinase complex. In this study, we investigated the relationship between dysbindin-1 and HDAC3. We found that dysbindin-1 formed a protein complex with HDAC3 in human neuroblastoma cells and in mouse brain. The interaction between dysbindin-1 and HDAC3 occurred in an isoform-specific manner: HDAC3 coupled with dysbindin-1A and -1B, but not -1C. We also found that dysbindin-1B expression was increased in the nucleus in the presence of HDAC3, and, conversely, that the phosphorylation level of HDAC3 increased in the presence of dysbindin-1B. Taken together, these results identify a novel binding partner for dysbindin-1, which may potentially provide a new avenue for research into the neurological mechanisms of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Neurosci. Lett. 2014 Oct 582: 120-4 |
| PMID | 25196196 |
| Title | Dysbindin-1, a schizophrenia-related protein, interacts with HDAC3. |
| Abstract | DTNBP1 is a key candidate gene associated with schizophrenia. The expression of its protein product, dysbindin-1, is altered in the brains of schizophrenic patients; however, the physiological functions of dysbindin-1 in the central nervous system are unclear. Several studies have shown that both dysbindin-1 and histone deacetylase 3 (HDAC3) can be phosphorylated by the DNA-dependent protein kinase complex. In this study, we investigated the relationship between dysbindin-1 and HDAC3. We found that dysbindin-1 formed a protein complex with HDAC3 in human neuroblastoma cells and in mouse brain. The interaction between dysbindin-1 and HDAC3 occurred in an isoform-specific manner: HDAC3 coupled with dysbindin-1A and -1B, but not -1C. We also found that dysbindin-1B expression was increased in the nucleus in the presence of HDAC3, and, conversely, that the phosphorylation level of HDAC3 increased in the presence of dysbindin-1B. Taken together, these results identify a novel binding partner for dysbindin-1, which may potentially provide a new avenue for research into the neurological mechanisms of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |