Background
Serotonin (5-HT) has been implicated in the pathophysiology of schizophrenia. Tryptophan
hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin (5-HT),
and as such it might be related to the pathogenesis of schizophrenia. Two isoforms
are known, TPH-1 and TPH-2. TPH-1 association with schizophrenia is debated.
Methods
A case-control design was employed for gene-disease association in 155 schizophrenic
psychosis patients and 253 healthy controls, all North European Caucasians. Six single
nucleotide polymorphisms (SNPs) with a haplotype block structure spanning over 23
kb of the total TPH-1 29 kb were analyzed. Linkage disequilibrium and haplotype analyses were performed.
Bonferroni correction was used for multiple testing.
Results
Single marker association analyses showed two SNPs significantly associated with schizophrenia.
Several haplotypes were associated with the disease. A “sliding window” analysis attributed
the strongest disease association to a haplotype configuration localized between the
promoter region and intron 3.
Conclusions
Our data indicate that TPH-1 associates with schizophrenia. It appears that specific combinations of promoter
variants vis-à-vis gene transcript variants contribute to genetic predisposition to
the disease.
Key Words
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Article info
Publication history
Published online: June 28, 2006
Accepted:
March 22,
2006
Received in revised form:
March 16,
2006
Received:
September 16,
2005
Identification
Copyright
© 2006 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
