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[5-羟色胺转运体(5-HTT)基因插入/缺失多态性与5-羟色胺受体2A(5HTR2A)基因T102C多态性与抑郁症患者对艾司西酞普兰和去甲替林的药物反应之间的关联]

[Association between polymorphisms of ins/del in the 5-HTT gene and T102C in the 5HTR2A gene and the drug response for escitalopram and nortriptyline in depressed patients].

作者信息

Rajewska-Rager Aleksandra, Dmitrzak-Weglarz Monika, Kapelski Paweł, Skibińska Maria, Kaczmarkiewicz-Fass Magdalena, Hauser Joanna

机构信息

Klinika Psychiatrii Dorosłych UM w Poznaniu.

出版信息

Psychiatr Pol. 2008 Nov-Dec;42(6):903-14.

Abstract

AIM

The role of the Serotonin receptor 5HT2A and Serotonin transporter 5HTTLPR polymorphisms was suggested in the pathogenesis of depression and the therapeutic response to serotonergic drugs. The aim of this study was to find a possible association between polymorphisms of ins/del in the 5-HTT gene and T102C in the 5HTR2A gene and drug response for escitalopram and nortriptyline in depressed patients.

METHOD

We analysed 90 patients (21 male and 69 females), in the age range 19-68 years, suffering from depressive disorder of at least moderate severity meeting the research criteria of ICD-10 and DSM-IV for major depression. All patients were part of the GENDEP study and were given the written consent for the study. The project was accepted by the local ethics committee. The subjects were randomized to one of the 2 different treatment regimes: (1) patients who received the serotoninergic drug--escitalopram (n=51) with a specified dose range of 10-20 mg/day. (2) patients treated by a noradrenergic drug--nortriptyline (n=39) with the dose range of 75-150 mg/day. The efficacy of treatment was defined by a reduction > or =50% of the total score of the Hamilton scale in the 8th week of treatment. Genotypes for polymorphisms of the ins/del 5-HTT gene and T102C 5HTR2A gene were established by the PCR-RFLP method in the Laboratory of Psychiatric Genetics of the Psychiatric Clinic. Statistical analysis was performed with Statistica version 7.1.

RESULTS

The results of the pharmacogenetic analysis, showed no association between the effects of serotoninergic (escitalopram) or noradrenergic (noradrenaline) therapy and the genotypes or alleles polymorphisms of the 5HTT and 5HTR2A genes.

摘要

目的

血清素受体5HT2A和血清素转运体5HTTLPR基因多态性在抑郁症发病机制及对血清素能药物的治疗反应中的作用已被提出。本研究的目的是寻找5 - HTT基因ins/del多态性和5HTR2A基因T102C多态性与抑郁症患者对艾司西酞普兰和去甲替林的药物反应之间可能存在的关联。

方法

我们分析了90名患者(21名男性和69名女性),年龄在19 - 68岁之间,患有至少中度严重程度的抑郁症,符合ICD - 10和DSM - IV关于重度抑郁症的研究标准。所有患者均为GENDEP研究的一部分,并已签署书面同意书。该项目获得当地伦理委员会批准。受试者被随机分为两种不同治疗方案之一:(1)接受血清素能药物——艾司西酞普兰(n = 51)的患者,指定剂量范围为10 - 20毫克/天。(2)接受去甲肾上腺素能药物——去甲替林(n = 39)治疗的患者,剂量范围为75 - 150毫克/天。治疗效果通过治疗第8周时汉密尔顿量表总分降低≥50%来定义。5 - HTT基因ins/del多态性和5HTR2A基因T102C多态性的基因型通过精神病学诊所精神病遗传学实验室的PCR - RFLP方法确定。使用Statistica 7.1版进行统计分析。

结果

药物遗传学分析结果显示,血清素能(艾司西酞普兰)或去甲肾上腺素能(去甲肾上腺素)治疗效果与5HTT和5HTR2A基因的基因型或等位基因多态性之间无关联。

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