Departamento de Investigación Neuroquímica, Hospital de Zamudio, Servicio Vasco de Salud, Zamudio, Vizcaya, Spain.
Neurochem Int. 2010 May-Jun;56(6-7):774-9. doi: 10.1016/j.neuint.2010.02.015. Epub 2010 Mar 4.
Metabolites of dopamine and norepinephrine measured in the plasma have long been associated with symptomatic severity and response to treatment in schizophrenic, bipolar and other psychiatric patients. Plasma concentrations of catecholamine metabolites are genetically regulated. The genes encoding enzymes that are involved in the synthesis and degradation of these monoamines are candidate targets for this genetic regulation. We have studied the relationship between the Val158Met polymorphism in catechol O-methyltransferase gene, variable tandem repeat polymorphisms in the monoamine oxidase A gene promoter, and plasma concentrations of 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid and homovanillic acid in healthy control subjects as well as in untreated schizophrenic and bipolar patients. We found that the Val158Met substitution in catechol O-methyltransferase gene influences the plasma concentrations of homovanillic and 3,4-dihydroxyphenylacetic acids. Although higher concentrations of plasma homovanillic acid were found in the high-activity ValVal genotype, this mutation did not affect the plasma concentration of 3-methoxy-4-hydroxyphenylglycol. 3,4-dihydroxyphenylacetic acid concentrations were higher in the low-activity MetMet genotype. Interestingly, plasma values 3-methoxy-4-hydroxyphenylglycol were greater in schizophrenic patients and in bipolar patients than in healthy controls. Our results are compatible with the previously reported effect of the Val158Met polymorphism on catechol O-methyltransferase enzymatic activity. Thus, our results suggest that this polymorphism, alone or associated with other polymorphisms, could have an important role in the genetic control of monoamine concentration and its metabolites.
多巴胺和去甲肾上腺素的代谢物在血浆中的水平与精神分裂症、双相情感障碍和其他精神疾病患者的症状严重程度和治疗反应长期相关。儿茶酚胺代谢物的血浆浓度受遗传调控。编码参与这些单胺类物质合成和降解的酶的基因是这种遗传调控的候选靶标。我们研究了儿茶酚氧位甲基转移酶基因中的 Val158Met 多态性、单胺氧化酶 A 基因启动子中的可变串联重复多态性与健康对照者以及未经治疗的精神分裂症和双相情感障碍患者的血浆 3-甲氧基-4-羟基苯乙二醇、3,4-二羟基苯乙酸和高香草酸浓度之间的关系。我们发现，儿茶酚氧位甲基转移酶基因中的 Val158Met 取代会影响高香草酸和 3,4-二羟基苯乙酸的血浆浓度。尽管高活性 ValVal 基因型的血浆高香草酸浓度较高，但这种突变并未影响 3-甲氧基-4-羟基苯乙二醇的血浆浓度。低活性 MetMet 基因型的 3,4-二羟基苯乙酸浓度较高。有趣的是，与健康对照组相比，精神分裂症患者和双相情感障碍患者的血浆 3-甲氧基-4-羟基苯乙二醇值更高。我们的结果与先前报道的 Val158Met 多态性对儿茶酚氧位甲基转移酶酶活性的影响一致。因此，我们的结果表明，这种多态性单独或与其他多态性一起，可能在单胺浓度及其代谢物的遗传控制中发挥重要作用。
