Jönsson E, Sedvall G, Brené S, Gustavsson J P, Geijer T, Terenius L, Crocq M A, Lannfelt L, Tylec A, Sokoloff P, Schwartz J C, Wiesel F A
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Biol Psychiatry. 1996 Nov 15;40(10):1032-43. doi: 10.1016/0006-3223(95)00581-1.
Monoamine metabolite (MM) levels in lumbar cerebrospinal fluid (CSF) are extensively used as indirect estimates of monoamine turnover in the brain. In this study we investigated genotypes for DNA polymorphisms in the D2 (DRD2), D3 (DRD3), and D4 (DRD4) dopamine receptor and tyrosine hydroxylase (TH) genes and their relationships to CSF MM in healthy volunteers (n = 66). Concentrations of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were corrected for back length, a confounding variable. Corrected MM levels were not related to age, gender, height, weight heredity, season or atmospheric pressure at sampling. Individuals with specific DRD2 and TH allele and genotype configurations significantly differed in HVA and MHPG concentrations. DRD3 homo- and heterozygotic genotypes had significantly different CSF 5-HIAA levels. DRD4 genotypes were not related to MM concentrations. The results suggest that specific DRD2, DRD3, and TH genotypes participate in the regulation of monoamine turnover in the central nervous system. Accordingly monoamine receptors and synthesizing enzyme genotypes appear to be variance factors influencing MM concentrations in CSF. The relationships found in this study support MM concentrations as markers for monoamine transmission in the human brain.
腰椎脑脊液（CSF）中的单胺代谢物（MM）水平被广泛用作大脑中单胺周转率的间接估计指标。在本研究中，我们调查了健康志愿者（n = 66）中多巴胺D2（DRD2）、D3（DRD3）和D4（DRD4）受体以及酪氨酸羟化酶（TH）基因的DNA多态性基因型，及其与脑脊液MM的关系。对高香草酸（HVA）、3-甲氧基-4-羟基苯乙二醇（MHPG）和5-羟吲哚乙酸（5-HIAA）的浓度进行了校正，以消除背长这一混杂变量的影响。校正后的MM水平与年龄、性别、身高、体重、遗传、季节或采样时的大气压力无关。具有特定DRD2和TH等位基因及基因型组合的个体，其HVA和MHPG浓度存在显著差异。DRD3纯合子和杂合子基因型的脑脊液5-HIAA水平有显著差异。DRD4基因型与MM浓度无关。结果表明，特定的DRD2、DRD3和TH基因型参与中枢神经系统中单胺周转率的调节。因此，单胺受体和合成酶基因型似乎是影响脑脊液中MM浓度的变异因素。本研究中发现的这些关系支持将MM浓度作为人类大脑中单胺传递的标志物。
