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

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-HT2AT102C 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. (C) 2008 Elsevier Ltd. All rights reserved.