Single nucleotide polymorphism and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene in suicide victims

Abstract

Background: Tryptophan hydroxylase, the rate-limiting enzyme in the biosynthesis of serotonin, represents a major candidate in numerous genetic association analyses of suicidal behavior; however, the results are so far inconclusive. Recently, a second tryptophan hydroxylase isoform (TPH2) was identified in mice, which was exclusively present in the brain. In a previous postmortem study of our own group, we could demonstrate that TPH2 is also expressed in the human brain but not in peripheral tissues.

Methods: We performed single nucleotide polymorphisms, haplotypes, and linkage disequilibrium studies on 263 suicide victims and 266 healthy control subjects with 10 single nucleotide polymorphisms in the TPH2 gene.

Results: Significant association was detected between one single nucleotide polymorphism (p = .004, global p = .01) and suicide. Additionally, haplotype analysis also produced support for association (p < .0001, global p = .0001).

Conclusions: This is the first report about an association between TPH2 gene polymorphisms and completed suicide. Our findings provide evidence for an involvement of genetic variants in the TPH2 gene in suicidal behavior. These results might open up new research strategies for the analysis of the observed disturbances in the serotonergic system in several other psychiatric disorders.