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ABCBl 单核苷酸多态性对抑郁症状严重程度和复发性抑郁障碍治疗效果的影响。

Importance of selected ABCB1 SNPs for the level of severity of depressive symptoms and effectiveness of recurrent depressive disorder therapy.

机构信息

Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1, Lodz 90-151, Poland.

Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1, Lodz 90-151, Poland.

出版信息

Gene. 2023 Jan 30;851:147021. doi: 10.1016/j.gene.2022.147021. Epub 2022 Nov 7.

Abstract

The expression level of mRNA and also the function of P-gp are strictly connected with the polymorphic nature of the ABCB1 gene. In this study, we evaluated the association between promoter SNP, i.e. T-129C, three other SNPs investigated earlier and ABCB1 expression in the depression group. To assess the additive significance of these SNPs on clinicopathological features a mathematical model was also built. 102 patients suffering from recurrent depressive disorder (rDD) and 94 healthy individuals from a local blood bank were enrolled in this study. ABCB1 gene polymorphism was identified by the RFLP method. The relative level of ABCB1 expression was measured by real-time PCR. For SNP T-129C no statistically significant differences in allele and genotype frequencies between depression and control groups were found (p = 0.3176). There was no statistically significant association between the expression value and 4 studied SNPs in ABCB1 (T-129C, C1236T, G2677T/A and C3435T) or the investigated clinicopathological features. Furthermore, a correlation between the initial HDRS score (lower than 23) and presence of at least 1236 T allele was observed, in particular in combination with 3435 T or 2677 T/A. Mutated allele of each SNP was also significantly associated with declined response to antidepressant therapy, both individually and in combination with others. Results of this study suggest that T-129C does not play an important role in the rDD development. The influence of the studied SNPs on ABCB1 gene expression is still unknown. However, the additive impact of 3 most frequently studied SNPs of ABCB1 on the course of depression and effectiveness of its treatment was confirmed.

摘要

mRNA 的表达水平以及 P-糖蛋白的功能与 ABCB1 基因的多态性密切相关。在这项研究中,我们评估了启动子 SNP(即 T-129C)、之前研究的另外三个 SNP 与抑郁症组中 ABCB1 表达之间的关联。为了评估这些 SNP 对临床病理特征的加性意义,还构建了一个数学模型。本研究纳入了 102 例复发性抑郁症(rDD)患者和 94 名来自当地血库的健康个体。通过 RFLP 方法鉴定 ABCB1 基因多态性。通过实时 PCR 测量 ABCB1 的相对表达水平。对于 SNP T-129C,在抑郁症组和对照组之间,等位基因和基因型频率没有统计学差异(p=0.3176)。在 ABCB1 中(T-129C、C1236T、G2677T/A 和 C3435T)或研究的临床病理特征中,未发现表达值与 4 个研究 SNP 之间存在统计学显著关联。此外,还观察到初始 HDRS 评分(低于 23)与至少存在 1236T 等位基因之间存在相关性,特别是与 3435T 或 2677T/A 组合时。每个 SNP 的突变等位基因也与抗抑郁治疗反应下降显著相关,无论是单独存在还是与其他 SNP 组合存在。本研究结果表明,T-129C 对 rDD 的发展不起重要作用。研究的 SNPs 对 ABCB1 基因表达的影响尚不清楚。然而,证实了 ABCB1 中 3 个最常研究的 SNP 对抑郁症病程和治疗效果的加性影响。

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