Haplotype-Based Linkage of Tryptophan Hydroxylase 2 to Suicide Attempt, Major Depression, and Cerebrospinal Fluid 5-Hydroxyindoleacetic Acid in 4 Populations

Abstract

Haplotype linkage of TPH2 to suicide attempt and major depression and to a mediating phenotype, cerebrospinal fluid 5-hydroxyindoleacetic acid, provides preliminary evidence of a functional locus potentially within a haplotype block at least 52 kb in size.

Functional promoter polymorphism of the neuronal isoform of tryptophan hydroxylase (Tph2) in suicide

“…Frequency of -703T allele of G-703T polymorphism in our control sample, being 20.4 %, fits well in the range of 18%-23%, reported for other Caucasian populations (Zhou et al, 2005;Reuter et al, 2007a;Zill et al, 2007). It should be noted that significantly higher frequencies of -703T allele were found in non-Caucasian populations such as African American (39%) (Zhou et al, 2005), American Indian (48%) (Zhou et al, 2005), Korean (57%) (Yoon et al, 2009) and Japanese (45%) (Mouri et al, 2009).…”

“…Nevertheless, our results, as well as findings on other populations (Zhou et al, 2005;Zill et al, 2007;Mouri et al, 2009), even ethnically very distant ones, clearly speak against the major role of functional variant G-703T of the Tph2 gene in the susceptibility to suicide.…”

“…Even when only violent suicide victims (N=282) were taken into consideration, no association was found (data not shown). The very recent study on suicide victims of Japanese origin (Mouri et al, 2009), as well as the two previous studies on suicide attempters (Zhou et al, 2005;Zill et al, 2007) also found no evidence for the effect of G-703T polymorphism on suicidal behavior. Yoon et al (2009), on the other hand, reported excess of GG homozygotes among suicidal depressed patients as compared to healthy controls.…”

“…It should be noted that significantly higher frequencies of -703T allele were found in non-Caucasian populations such as African American (39%) (Zhou et al, 2005), American Indian (48%) (Zhou et al, 2005), Korean (57%) (Yoon et al, 2009) and Japanese (45%) (Mouri et al, 2009).…”

Tryptophan hydroxylase 2 (TPH2) haplotypes predict levels of TPH2 mRNA expression in human pons

“…17 The frequencies of haplotypes within each block are listed in Figure S2B, and the predicted diplotypes for each individual in our collection are listed in Table S1 in Supplemental materials. The possible contribution of each SNP to TPH2 mRNA AEI was evaluated by looking for correlations between heterozygosity/homozygosity of the SNP and the presence/absence of AEI for TPH2 mRNA within the 27 samples where AEI measurements were made.…”