title: Methylation and QTDT analysis of the 5-HT2A receptor 102C allele: analysis of suicidality in major psychosis.
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.
authors.affiliation: Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College Road, Toronto, Ontario, Canada.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
authors.forename: Emanuela
authors.initials: E
authors.lastname: Viggiano
authors.forename: Ranbir
authors.initials: R
authors.lastname: Dhoot
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: Albert H C
authors.initials: AH
authors.lastname: Wong
mesh_terms: D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics / Q000523:psychology; D006801:Humans; D007962:Leukocytes; D008297:Male; D008745:Methylation; D016133:Polymerase Chain Reaction / Q000379:methods / Q000706:statistics & numerical data; D011110:Polymorphism, Genetic / Q000235:genetics; D017397:Prefrontal Cortex; D011618:Psychotic Disorders / Q000235:genetics* / Q000523:psychology; D019655:Quantitative Trait, Heritable; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics; D012565:Schizophrenic Psychology; D013405:Suicide / Q000523:psychology / Q000706:statistics & numerical data
chemical_list: D044402:Receptor, Serotonin, 5-HT2A