Levchenko Anastasia, Losenkov Innokentiy S, Vyalova Natalia M, Simutkin German G, Bokhan Nikolay A, Wilffert Bob, Loonen Anton Jm, Ivanova Svetlana A
Institute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg, Russia,
Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia.
Pharmgenomics Pers Med. 2018 Jul 20;11:121-126. doi: 10.2147/PGPM.S171423. eCollection 2018.
and genes have been implicated in the pathogenesis of a number of psychiatric and neurological disorders. Furthermore, their genetic variants are associated with response to antidepressant pharmacotherapy. As the evidence is still incomplete and inconsistent, continuing efforts to investigate the role of these two genes in the pathogenesis and treatment of brain disorders is necessary. The aim of our study was thus to evaluate the association of variants of these two genes with depressive disorders and drug treatment response.
In the present study, 222 patients with a depressive disorder who underwent pharmacological antidepressant treatment were divided into remitters and non-remitters following a 28-day course of pharmacotherapy. The association of a depressive disorder and remission rates with polymorphisms rs334558 in the gene and rs1130214 and rs3730358 in the gene was evaluated with a chi-square test.
Neither of the studied genetic variants was associated with a depressive disorder. Furthermore, frequencies of alleles and genotypes for rs1130214 and rs3730358 were not different in the groups of remitters and non-remitters. However, the activating allele T of the functional polymorphism rs334558 was significantly associated with remission, when all types of antidepressant drugs were included. This association continued as a trend when only patients taking selective serotonin reuptake inhibitors were considered.
The present study provides support that the functional polymorphism rs334558 of may play a role as a useful genetic and pharmacogenetic biomarker in the framework of personalized medicine approach.
基因和基因已被认为与多种精神和神经疾病的发病机制有关。此外,它们的基因变异与抗抑郁药物治疗的反应相关。由于证据仍不完整且不一致,因此有必要继续努力研究这两个基因在脑部疾病发病机制和治疗中的作用。因此,我们研究的目的是评估这两个基因的变异与抑郁症及药物治疗反应之间的关联。
在本研究中,222例接受抗抑郁药物治疗的抑郁症患者在进行28天的药物治疗后被分为缓解者和未缓解者。采用卡方检验评估抑郁症及缓解率与基因中rs334558多态性以及基因中rs1130214和rs3730358多态性之间的关联。
所研究的基因变异均与抑郁症无关。此外,rs1130214和rs3730358的等位基因和基因型频率在缓解者和未缓解者组中并无差异。然而,当纳入所有类型的抗抑郁药物时,功能性多态性rs334558的激活等位基因T与缓解显著相关。当仅考虑服用选择性5-羟色胺再摄取抑制剂的患者时,这种关联仍呈趋势。
本研究支持基因的功能性多态性rs334558在个性化医疗方法框架中可能作为一种有用的遗传和药物遗传生物标志物发挥作用。