SNP and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene provide evidence for association with major depression
Abstract
Tryptophan hydroxylase (TPH), being the rate-limiting enzyme in the biosynthesis of serotonin plays a major role as candidate gene in several psychiatric disorders. Recently, a second TPH isoform (TPH2) was identified in mice, which was exclusively present in the brain. In a previous post-mortem study of our own group, we could demonstrate that TPH2 is also expressed in the human brain, but not in peripheral tissues. This is the first report of an association study between polymorphisms in the TPH2 gene and major depression (MD). We performed single-nucleotide polymorphism (SNP), haplotype and linkage disequlibrium studies on 300 depressed patients and 265 healthy controls with 10 SNPs in the TPH2 gene. Significant association was detected between one SNP (P=0.0012, global P=0.0051) and MD. Haplotype analysis produced additional support for association (P<0.0001, global P=0.0001). Our findings provide evidence for an involvement of genetic variants of the TPH2 gene in the pathogenesis of MD and might be a hint on the repeatedly discussed duality of the serotonergic system. These results may open up new research strategies for the analysis of the observed disturbances in the serotonergic system in patients suffering from several other psychiatric disorders.
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Zill et al. and Zhang et al. groups reported genetic modifications that could link TPH2 gene to DD susceptibility.
“In this way, both Zill et al. [232] and Zhang et al. [233] groups reported genetic modifications that could link TPH2 gene to DD susceptibility.”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [232]
A specific brain isoform of tryptophan hydroxylase (TPH2) may be the connection between serotonergic systems and depression and BD.
“It seems also that a specific brain isoform of tryptophan hydroxylase (TPH2) may be the connection between serotonergic systems and depression and BD [232].”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [232]
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- Authors
- Zill, P., Baghai, T. C., Zwanzger, P., Schüle, C., Eser, D., Rupprecht, R., Möller, H.-J., Bondy, B., & Ackenheil, M.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- Corresponding author
- Zill, P
- Venue
- Molecular Psychiatry
- Published
- 2004-05-04
- Volume
- 9
- Issue
- 11
- Pages
- 1030-1036
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2077425100
- Cited by
- 323
- References
- 29
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 1 · 2023: 6 · 2022: 7 · 2021: 10 · 2020: 8 · 2019: 10 · 2018: 6 · 2017: 9 · 2016: 10 · 2015: 12 · 2014: 13 · 2013: 17 · 2012: 22
- FWCI
- 14.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- tryptophan hydroxylase 2, TPH2 gene, major depressive disorder, single nucleotide polymorphisms, haplotype analysis, linkage disequilibrium, genetic association, serotonin synthesis, serotonergic system, brain-specific expression, candidate genes
- MeSH terms
- Adult, Brain, Chromosomes, Human, Pair 12, Major Depressive Disorder, Female, Gene Frequency, Haplotypes, Humans, Isoenzymes, Lod Score, Male, Middle Aged, Serotonin, Tryptophan Hydroxylase, Linkage Disequilibrium, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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