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