Differential expression and parent-of-origin effect of the 5-HT2A receptor gene C102T polymorphism: analysis of suicidality in schizophrenia and bipolar disorder.
The serotonin 2A (5-HT2A) receptor gene has been implicated in the pathogenesis of suicidal behavior by a genetic association between the 5-HT2A C102T silent polymorphism and suicidality in patients with major depression. However, a recent meta-analysis failed to confirm this association. We developed an improved quantitative assay for the measurement of allele-specific expression of the 5-HT2A gene, and find that the ratio of C/T allele expression in the pre-frontal cortex of heterozygous suicide victims (n = 10) was significantly decreased in comparison with the non-suicide group (n = 10) (P = 0.049). Because the 5-HT2A gene is subject to imprinting, the parent-of-origin may affect the inheritance of suicidal behavior. 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 behavior was available. No association between the 5-HT2A C102T polymorphism and suicidal behavior in major psychoses was detected with the transmission/disequilibrium test (TDT).
De Luca
Vincenzo
V
Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Likhodi
Olga
O
Kennedy
James L
JL
Wong
Albert H C
AH
D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D008040:Genetic Linkage; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D008875:Middle Aged; D010290:Parents; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000032:analysis; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D013405:Suicide
D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A