期刊
PSYCHIATRY RESEARCH
卷 180, 期 2-3, 页码 63-67出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.psychres.2009.11.018
关键词
Genetics; Cerebrospinal fluid (CSF); 5-hydroxyindoleacetic acid (5-HIAA); Homovanillic acid (HVA); 3-merhoxy-4-hydroxyphenylglycol (MHPG)
类别
资金
- Swedish Research Council [2006-2992, 2006-986, 2008-2167]
- HUBIN
- Copenhagen Hospital Corporation Research Fund
- Danish National Psychiatric Research Foundation
- Danish Agency for Science, and Technology and Innovation (Centre for Pharmacogenetics)
- Research Council of Norway [147787, 167153]
- Eastern Norway Health Authority [RHF 123/2004]
- Ulleval University Hospital
- University of Oslo
- Uppsala University
- Uppsala University Hospital
- Knut and Alice Wallenberg Foundation
Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin synthesis. We investigated possible relationships between five TPH1 gene polymorphisms and cerebrospinal fluid (CSF) concentrations of the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the major dopamine metabolite homovanillic acid (HVA), and the major norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 132). The G-allele of the TPH1 rs4537731 (A-6526G) polymorphism was associated with 5-HIM and HVA, but not MHPG concentrations. None of the other four TPH1 polymorphisms (rs211105, rs1800532, rs1799913 and rs7933505) were significantly associated with any of the monoamine metabolite concentrations. Two (rs4537731G/rs211105T/rs1800532C/rs1799913C/rs7933505G and rs4537731A/rs211105T/rs1800532C/rs1799913C/rs7933505G) of five common TPH1 five-allele haplotypes were associated with 5-HIAA and HVA concentrations in opposite directions. None of the common haplotypes was associated with MHPG concentrations in the CSF. The results suggest that TPH1 gene variation participates in the regulation of serotonin and dopamine turnover rates in the central nervous system of healthy human subjects. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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