Laboratory of Recognition Biology, North Fluminense State University (UENF), Campos dos Goytacazes, RJ, Brazil.
Laboratory of Reproduction and Animal Breeding - LRMGA, Center for Agricultural Technological Sciences - CCTA, North Fluminense State University, Campos do Goytacazes, Brazil.
J Affect Disord. 2019 Feb 15;245:716-723. doi: 10.1016/j.jad.2018.10.369. Epub 2018 Nov 6.
Genetic and epigenetic variations of the serotonin transporter gene (SLC6A4) have been related to the etiology of depression. The 5-HTTLPR polymorphism at the SLC6A4 promoter region has two variants, a short allele (S) and a long allele (L), in which the S allele results in lower gene transcription and has been associated with depression. The short S-allele of 5-HTTLPR polymorphism of this gene has been associated with depression. In addition to molecular mechanisms, exposure to early life risk factors such as maternal depression seems to affect the development of depression in postnatal life. The present study investigated the association of 5-HTTLPR polymorphism and CpG DNA methylation (5mC) levels of an AluJb repeat element at the SLC6A4 promoter region in mother-child pairs exposed to maternal depression.
We analyzed DNA samples from 60 subjects (30 mother-child pairs) split into three groups, with and without major depression disorder (DSM-IV) among children and mothers. The genotyping of 5-HTTLPR polymorphism and quantification of 5mC levels was performed by qualitative PCR and methylation-sensitive restriction enzyme digestion, and real-time quantitative PCR (MSRED-qPCR), respectively.
The sample analyzed presented a higher frequency of S allele of 5-HTTLPR (67.5%). Despite the high frequency of this allele, we did not find statistically significant differences between individuals carrying at least one S allele between the depression and healthy control subjects, or among the mother-child pair groups with different patterns of occurrence of depression. In the group where the mother and child were both diagnosed with depression, we found a statistically significant decrease of the 5mC level at the SLC6A4 promoter region.
The limitations are the relatively small sample size and lack of gene expression data available for comparison with methylation data.
In this study, we demonstrated a repeat element specific 5mC level reduction in mother-child pairs, concordant for the diagnosis of depression.
5-羟色胺转运体基因（SLC6A4）的遗传和表观遗传变异与抑郁症的病因有关。SLC6A4 启动子区域的 5-HTTLPR 多态性有两种变体，短等位基因（S）和长等位基因（L），其中 S 等位基因导致基因转录减少，并与抑郁症有关。该基因的 5-HTTLPR 多态性的短 S 等位基因与抑郁症有关。除了分子机制外，暴露于母体抑郁等早期生活风险因素似乎会影响产后生活中抑郁症的发展。本研究调查了暴露于母体抑郁的母子对中 SLC6A4 启动子区域的 5-HTTLPR 多态性和 AluJb 重复元件的 CpG DNA 甲基化（5mC）水平的关联。
我们分析了来自 60 个样本（30 对母子）的 DNA 样本，这些样本分为三组，儿童和母亲中有无重性抑郁障碍（DSM-IV）。通过定性 PCR 和甲基化敏感限制性内切酶消化，以及实时定量 PCR（MSRED-qPCR）分别对 5-HTTLPR 多态性和 5mC 水平的定量进行分析。
分析的样本中 S 等位基因的 5-HTTLPR 频率较高（67.5%）。尽管这种等位基因的频率较高，但我们没有发现携带至少一个 S 等位基因的个体在抑郁和健康对照组之间或在不同发生模式的母子对组之间存在统计学上的显著差异。在母亲和孩子都被诊断为抑郁症的组中，我们发现 SLC6A4 启动子区域的 5mC 水平有统计学显著下降。
局限性是样本量相对较小，并且缺乏与甲基化数据进行比较的基因表达数据。
在这项研究中，我们证明了重复元件特异性的 5mC 水平降低在母子对中，与抑郁症的诊断一致。
