Methylation and QTDT analysis of the 5-HT2A receptor 102C allele: Analysis of suicidality in major psychosis

ArticleinJournal of Psychiatric Research 43(5):532-7 · October 2008with28 Reads
DOI: 10.1016/j.jpsychires.2008.07.007 · Source: PubMed
Abstract
Suicide is an act deliberately initiated and performed by a person with full knowledge that a fatal outcome is probable. The serotonin 2A (5-HT2A) receptor gene has been implicated in the pathogenesis of suicidal behaviour by a genetic association between the 5-HT2A T102C silent polymorphism and suicidality in patients with mood disorders and schizophrenia. However, a recent meta-analysis failed to confirm this association. We developed an improved quantitative assay for the measurement of allele-specific methylation of the 5-HT2A gene, and found that the methylation of the C allele in the pre-frontal cortex of heterozygous suicide victims (n=10) was not significantly different in comparison with the non-suicide group (n=10) (p=0.084). We also analyzed methylation of the C allele in white blood cell DNA from bipolar and schizophrenic attempters and found a significant difference in the schizophrenic attempters (p=0.00013) but not in the bipolar attempters (p=0.616). Because the 5-HT2A gene is subject to imprinting, the parent-of-origin may affect inheritance of suicidal behaviour. Thus, we examined the parental origin of specific alleles for genetic association in a genetic family-based sample of major psychoses in which information on suicidal behaviour was available. This result suggests that methylation of the 102C allele does not influence completed suicide.
    • "5-HT2A receptor (HTR2A) gene is a serotonergic system gene and in a study it was found that methylation of the HTR2A gene promoter correlated with HTR2A expression levels. However, another study found no difference between schizophrenia patients compared to controls in HTR2A meth- ylation [44,45]. Epigenetic regulations of genes influencing the dopaminergic system, such as COMT, DRD2, and DAT genes, have been investigated in schizophrenia. "
    Dataset · Feb 2016 · Australian and New Zealand Journal of Psychiatry
    • "5-HT2A receptor (HTR2A) gene is a serotonergic system gene and in a study it was found that methylation of the HTR2A gene promoter correlated with HTR2A expression levels. However, another study found no difference between schizophrenia patients compared to controls in HTR2A meth- ylation [44,45]. Epigenetic regulations of genes influencing the dopaminergic system, such as COMT, DRD2, and DAT genes, have been investigated in schizophrenia. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Although genetic factors are risk factors for schizophrenia, some environmental factors are thought to be required for the manifestation of disease. Epigenetic mechanisms regulate gene functions without causing a change in the nucleotide sequence of DNA. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that regulates synaptic transmission and plasticity. It has been suggested that BDNF may play a role in the pathophysiology of schizophrenia. It is established that methylation status of the BDNF gene is associated with fear learning, memory, and stressful social interactions. In this study, we aimed to investigate the DNA methylation status of BDNF gene in patients with schizophrenia. Material/Methods The study included 49 patients (33 male and 16 female) with schizophrenia and 65 unrelated healthy controls (46 male and 19 female). Determination of methylation pattern of CpG islands was based on the principle that bisulfite treatment of DNA results in conversion of unmethylated cytosine residues into uracil, whereas methylated cytosine residues remain unmodified. Methylation-specific PCR was performed with primers specific for either methylated or unmethylated DNA. Results There was no significant difference in methylated or un-methylated status for BDNF promoters between schizophrenia patients and controls. The mean duration of illness was significantly lower in the hemi-methylated group compared to the non-methylated group for BDNF gene CpG island-1 in schizophrenia patients. Conclusions Although there were no differences in BDNF gene methylation status between schizophrenia patients and healthy controls, there was an association between duration of illness and DNA methylation.
    Full-text · Article · Feb 2016
    • "@BULLETBDNF Met allele and Met/Met genotype @BULLETSNPs on 2p25 fall in a large linkage disequilibrium block containing the ACP1 (acid phosphatase 1) gene @BULLETHaplotypes of the FKBP5 gene @BULLETIMPA2 (rs669838 AA genotype) @BULLETINPPI (rs4853694 GG genotype) @BULLETGSK3β (rs1732170 T allele; rs119221360 A allele) @BULLETLinkage signal at 2p12 at marker D2S1777 @BULLETZNF804A (rs1344706A allele) @BULLETTrend towards associaaon between ANK3 (rs9804190T allele) @BULLETHigher severity of suicidal behaviour (measured as a connnuous variable) associated with CRH receptor 2 haplotype 5-2-3 Altamura et al. (2010), Baumann et al. (1999), Bellivier et al. (2000), Benedetti et al. (2011), Berrettini et al. (1986), Campos et al. (2010, D'Ambrosio et al. (2012), De Luca et al. (2005a Luca et al. ( , 2005b Luca et al. ( , 2006 Luca et al. ( , 2009), Dowlatshahi et al. (1999) "
    [Show abstract] [Hide abstract] ABSTRACT: Bipolar disorder is associated with elevated risk of suicide attempts and deaths. Key aims of the International Society for Bipolar Disorders Task Force on Suicide included examining the extant literature on epidemiology, neurobiology and pharmacotherapy related to suicide attempts and deaths in bipolar disorder. Systematic review of studies from 1 January 1980 to 30 May 2014 examining suicide attempts or deaths in bipolar disorder, with a specific focus on the incidence and characterization of suicide attempts and deaths, genetic and non-genetic biological studies and pharmacotherapy studies specific to bipolar disorder. We conducted pooled, weighted analyses of suicide rates. The pooled suicide rate in bipolar disorder is 164 per 100,000 person-years (95% confidence interval = [5, 324]). Sex-specific data on suicide rates identified a 1.7:1 ratio in men compared to women. People with bipolar disorder account for 3.4-14% of all suicide deaths, with self-poisoning and hanging being the most common methods. Epidemiological studies report that 23-26% of people with bipolar disorder attempt suicide, with higher rates in clinical samples. There are numerous genetic associations with suicide attempts and deaths in bipolar disorder, but few replication studies. Data on treatment with lithium or anticonvulsants are strongly suggestive for prevention of suicide attempts and deaths, but additional data are required before relative anti-suicide effects can be confirmed. There were limited data on potential anti-suicide effects of treatment with antipsychotics or antidepressants. This analysis identified a lower estimated suicide rate in bipolar disorder than what was previously published. Understanding the overall risk of suicide deaths and attempts, and the most common methods, are important building blocks to greater awareness and improved interventions for suicide prevention in bipolar disorder. Replication of genetic findings and stronger prospective data on treatment options are required before more decisive conclusions can be made regarding the neurobiology and specific treatment of suicide risk in bipolar disorder. © The Royal Australian and New Zealand College of Psychiatrists 2015.
    Full-text · Article · Jul 2015
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