Department of Clinical Neuroscience, HUBIN project, Karolinska Institutet and Hospital, R5:00, SE-171 76 Stockholm, Sweden.
Psychiatry Res. 2010 Dec 30;180(2-3):63-7. doi: 10.1016/j.psychres.2009.11.018. Epub 2010 May 23.
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-HIAA 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.
色氨酸羟化酶（TPH）是 5-羟色胺合成中的限速酶。我们研究了五个 TPH1 基因多态性与健康志愿者脑脊液（CSF）中 5-羟吲哚乙酸（5-HIAA，主要 5-羟色胺代谢物）、高香草酸（HVA，主要多巴胺代谢物）和 3-甲氧基-4-羟苯乙二醇（MHPG，主要去甲肾上腺素代谢物）浓度之间的可能关系。TPH1 rs4537731（A-6526G）多态性的 G 等位基因与 5-HIAA 和 HVA 相关，但与 MHPG 浓度无关。其他四个 TPH1 多态性（rs211105、rs1800532、rs1799913 和 rs7933505）与任何单胺代谢物浓度均无显著相关性。五个常见的 TPH1 五等位基因单倍型中有两个（rs4537731G/rs211105T/rs1800532C/rs1799913C/rs7933505G 和 rs4537731A/rs211105T/rs1800532C/rs1799913C/rs7933505G）与 5-HIAA 和 HVA 浓度呈相反方向相关。常见单倍型均与 CSF 中的 MHPG 浓度无关。结果表明，TPH1 基因变异参与了健康人体中枢神经系统中 5-羟色胺和多巴胺周转率的调节。
