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.
Key words
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Article info
Publication history
Published online: September 21, 2004
Accepted:
July 23,
2004
Received in revised form:
June 23,
2004
Received:
February 25,
2004
Identification
Copyright
© 2004 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
