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ABCB1基因C3435T多态性对波兰人群抑郁症遗传易感性及治疗反应的影响——初步报告

The Influence of C3435T Polymorphism of the ABCB1 Gene on Genetic Susceptibility to Depression and Treatment Response in Polish Population - Preliminary Report.

作者信息

Jeleń Agnieszka Maria, Sałagacka Aleksandra, Żebrowska Marta Karolina, Mirowski Marek, Talarowska Monika, Gałecki Piotr, Balcerczak Ewa Izabela

机构信息

1. Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Interdepartmental Chair of Laboratory and Molecular Diagnostics, Medical University of Lodz, Poland.

2. Department of Adult Psychiatry, Medical University of Lodz, Poland.

出版信息

Int J Med Sci. 2015 Nov 20;12(12):974-9. doi: 10.7150/ijms.13119. eCollection 2015.

Abstract

BACKGROUND

Despite the high prevalence of depression, the mechanism of the origin of this disease as well as the causes of resistance to therapy in some patients are still not fully understood. Increasingly, the possible role of genetic factors is considered. One of them is polymorphisms in the ABCB1 (MDR1) gene which encodes P-glycoprotein, responsible for the transport of xenobiotics, including antidepressant drugs, through the blood-brain barrier.

METHODS

C3435T was evaluated in 90 patients with recurrent depressive disorders (rDD). Genotyping was performed using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).

RESULTS

The obtained results indicate that the TT genotype occurred more frequently among patients with rDD than in healthy volunteers (p=0.0441). Also, at least one C allele was present significantly less frequent in the study group than in healthy individuals (p=0.0300). The severity of depressive symptoms was higher among patient with the CC genotype in comparison with the other genotypes (p=0.0106) but treatment response to antidepressants was better in this group than among patients with CT or TT genotypes (p=0.0301). Likewise, patients with the T allele have a significantly lower severity of symptoms (p=0.0026) and decreased therapy effectiveness (p=0.0142) than C allele carriers.

CONCLUSIONS

This study suggests that C3435T polymorphisms in the ABCB1 gene are strongly associated with a predisposition to depression development, the severity of depressive symptoms and the effectiveness of therapy with using different groups of antidepressant agents.

摘要

背景

尽管抑郁症患病率很高,但该疾病的发病机制以及部分患者治疗抵抗的原因仍未完全明确。人们越来越多地考虑遗传因素的可能作用。其中之一是ABCB1(MDR1)基因的多态性,该基因编码P-糖蛋白,负责包括抗抑郁药物在内的外源性物质通过血脑屏障的转运。

方法

对90例复发性抑郁症(rDD)患者进行C3435T评估。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)进行基因分型。

结果

所得结果表明,rDD患者中TT基因型的出现频率高于健康志愿者(p = 0.0441)。此外,研究组中至少有一个C等位基因的出现频率显著低于健康个体(p = 0.0300)。与其他基因型相比,CC基因型患者的抑郁症状严重程度更高(p = 0.0106),但该组对抗抑郁药的治疗反应优于CT或TT基因型患者(p = 0.0301)。同样,与C等位基因携带者相比,携带T等位基因的患者症状严重程度显著更低(p = 0.0026),治疗效果降低(p = 0.0142)。

结论

本研究表明,ABCB1基因的C3435T多态性与抑郁症发病易感性、抑郁症状严重程度以及不同组抗抑郁药治疗效果密切相关。

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