Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Am J Med Genet B Neuropsychiatr Genet. 2010 Sep;153B(6):1160-6. doi: 10.1002/ajmg.b.31081.
Cytochrome P450 2C19 (CYP2C19) is a polymorphic enzyme active in the metabolism of for example diazepam and the antidepressants sertraline, citalopram, and escitalopram, whereby allelic variants cause increased (CYP2C1917) or abolished (mainly CYP2C192) enzymatic activity in drug metabolism. In light of the importance of CYP2C19 in the metabolism of psychoactive substances we considered it of interest to investigate the relationship between CYP2C19 polymorphisms and depressive symptoms in 1,472 subjects of European ancestry (45-98 years old) from the Swedish Twin Registry. Depressive symptoms were assessed using the Center of Epidemiologic Studies Depression (CES-D) scale. We found that poor metabolizers lacking CYP2C19 activity (PMs, CYP2C19*2/2) had significantly lower levels of depressive symptoms than extensive metabolizers (EMs, CYP2C191/*1) (P = 0.0018). The size of this difference was in the same range as that between subjects reported taking antidepressants (n = 104) and those without antidepressant treatment (P < 0.0001). Our results suggest for the first time that the CYP2C19 polymorphism might be of importance for depressive symptoms, as here shown for older European adults.
细胞色素 P450 2C19（CYP2C19）是一种多态酶，在例如地西泮和抗抑郁药舍曲林、西酞普兰和艾司西酞普兰的代谢中具有活性，其中等位基因变体导致药物代谢中酶活性增加（CYP2C1917）或消除（主要是 CYP2C192）。鉴于 CYP2C19 在精神活性物质代谢中的重要性，我们认为研究 CYP2C19 多态性与来自瑞典双胞胎登记处的 1472 名欧洲血统个体（45-98 岁）的抑郁症状之间的关系很有意义。使用流行病学研究抑郁量表（CES-D）评估抑郁症状。我们发现缺乏 CYP2C19 活性的弱代谢者（PM，CYP2C19*2/2）的抑郁症状水平明显低于广泛代谢者（EM，CYP2C191/*1）（P = 0.0018）。这种差异的大小与报告服用抗抑郁药（n = 104）和未接受抗抑郁治疗的受试者之间的差异相同（P < 0.0001）。我们的结果首次表明，CYP2C19 多态性可能对抑郁症状很重要，正如这里所示，对于年龄较大的欧洲成年人。
