Depression in systemic lupus erythematosus patients is associated with link-polymorphism but not methylation status of the 5HTT promoter region
Depression in systemic lupus erythematosus patients is associated with link-polymorphism but not methylation status of the 5HTT promoter region
复制标题
系统性红斑狼疮患者的抑郁症与链接多态性相关，但与 5HTT 启动子区域的甲基化状态无关
DOI：
10.1177/0961203313498793
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发表时间：
2013-09-01
期刊：
影响因子：
2.6
通讯作者：
Zeng, X. F.
中科院分区：
文献类型：
--
作者：
Xu, J.;Cheng, Y. Q.;Zeng, X. F.
据报道，系统性红斑狼疮（SLE）患者中抑郁症的患病率较高，然而这一现象背后的机制仍不清楚。本研究从遗传学和表观遗传学的角度探讨了5 - 羟色胺转运体基因（5HTT）启动子区域（PR - 5HTT）的多态性和甲基化状态是否与SLE患者的抑郁症有关。在这项研究中，招募了96名SLE患者和96名健康对照者（HCs）。使用汉密尔顿抑郁评定量表（HDRS）评估所有受试者的抑郁水平。在SLE患者和健康对照者的外周淋巴细胞中检测5 - 羟色胺转运体相关多态性（5HTTLPR）以及PR - 5HTT的DNA甲基化状态。比较了SLE患者和健康对照者之间5HTTLPR和PR - 5HTT的DNA甲基化的差异。在SLE患者中，抑郁的SLE（SLE - D）患者中5HTTLPR的短等位基因（S）和SS基因型频率高于非抑郁的SLE（SLE - ND）患者。SS纯合子患者的平均HDRS评分高于SL/LL基因型患者。相反，PR - 5HTT在健康对照者以及SLE患者中均呈低甲基化。健康对照者和SLE患者之间的甲基化状态没有差异。因此，PR - 5HTT的功能表达可能主要受基因多态性调控，而非DNA甲基化。5HTTLPR的风险等位基因似乎是SLE患者抑郁症的主要促成因素。
A higher prevalence of depression in systemic lupus erythematosus (SLE) patients has been reported, though the mechanism underlying this phenomenon remains unclear. The present study was conducted to explore whether the polymorphism and methylation status of the serotonin transporter gene (5HTT) promoter region (PR-5HTT) contribute to depression in SLE patients from both genetic and epigenetic perspectives. In this study, 96 SLE patients and 96 healthy controls (HCs) were recruited. Depression levels of all subjects were evaluated using the Hamilton Depression Rating Scale (HDRS). The serotonin transporter-linked polymorphism (5HTTLPR) and the DNA methylation status of PR-5HTT were detected in peripheral lymphocytes of SLE patients and HCs. The differences in 5HTTLPR and DNA methylation of PR-5HTT between SLEs and HCs were compared. In SLE patients, the frequencies of short allele (S) and SS genotype of 5HTTLPR were higher in depressive SLE (SLE-D) patients than in non-depressive SLE (SLE-ND) patients. The mean HDRS score of SS homozygote patients was higher than that of patients with SL/LL genotypes. Conversely, PR-5HTT was hypomethylated in HCs as well as SLE patients. There was no difference in the methylation status between HCs and SLEs. Thus, the functional expression of PR-5HTT may be primarily regulated by gene polymorphism and not by DNA methylation. The risk allele of 5HTTLPR appears to be a major contributor to depression in SLE patients.