title: The interaction between TPH2 promoter haplotypes and clinical-demographic risk factors in suicide victims with major psychoses.
abstract: Tryptophan hydroxylase isoform 2 (TPH2) is a rate-limiting enzyme in the biosynthesis of serotonin (5-HT) and is predominantly localized in the brain. Previous studies have suggested that there is an association between serotonergic dysfunction in the brain and suicidality. This study was designed to examine whether the -473T > A and -8396G > C polymorphisms of the TPH2 gene may be associated with completed suicide in subjects with major psychoses from the Stanley Foundation Brain Bank sample. TPH2 genotypes were determined in 69 subjects with a diagnosis of schizophrenia or bipolar disorder, among which 22 died by suicide. Genomic DNA was amplified by polymerase chain reaction and typed by automated methods. Both markers were found to be in Hardy-Weinberg equilibrium and in strong linkage disequilibrium. No association with history of suicide was found for either polymorphism. Haplotype analysis with EHAP showed no association between completed suicide and haplotype distribution (chi2 = 1.877; 3 df; P = 0.598). Nor was there any association between suicide and these genetic markers even when clinical-demographic factors were considered as covariates in the haplotype analysis. These findings suggest that these 5' marker haplotypes in the TPH2 gene do not influence suicidal behaviour.
authors.affiliation: Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: V
authors.initials: V
authors.lastname: De Luca
authors.forename: D
authors.initials: D
authors.lastname: Hlousek
authors.forename: O
authors.initials: O
authors.lastname: Likhodi
authors.forename: H H M
authors.initials: HH
authors.lastname: Van Tol
authors.forename: J L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: A H C
authors.initials: AH
authors.lastname: Wong
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics* / Q000378:metabolism; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics* / Q000401:mortality; D013405:Suicide; D014365:Tryptophan Hydroxylase / Q000235:genetics*
chemical_list: D007527:Isoenzymes; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase