Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Statistics and Data Center, Samsung Medical Center, Seoul, South Korea.
Am J Med Genet B Neuropsychiatr Genet. 2023 Jan;192(1-2):28-37. doi: 10.1002/ajmg.b.32921. Epub 2022 Sep 12.
Genetic variation of the serotonin transporter gene (SLC6A4) has been suggested as potential mediator for antidepressant response in patients with depression. This study aimed to determine whether DNA methylation in SLC6A4 changes after antidepressant treatment and whether it affects treatment response in patients with depression. Overall, 221 Korean patients with depression completed 6 weeks of selective serotonin reuptake inhibitor (SSRI) monotherapy. DNA was extracted from venous blood pre- and post-treatment, and DNA methylation was analyzed using polymerase chain reaction. We used Wilcoxon's signed-rank test to verify the difference in methylation after treatment. Treatment response was assessed using the 17-item Hamilton Depression Rating Scale, and mRNA levels were quantified. After adjusting for relevant covariates, DNA methylation was significantly altered in specific CpG sites in SLC6A4 (p < .001 in CpG3, CpG4, and CpG5) following 6 weeks of treatment. Methylation change's magnitude (ΔDNA methylation) after drug treatment was not associated with treatment response or mRNA level change. SSRI antidepressants can influence SLC6A4 methylation in patients with depression. However, ΔDNA methylation at CpG3, CpG4, and CpG5 in SLC6A4 was not associated with treatment response. Future studies should investigate the integrative effect of other genetic variants and CpG methylation on gene transcription and antidepressant treatment response.
基因变异的 5-羟色胺转运体基因（SLC6A4）被认为是潜在的调解人 抗抑郁药反应在抑郁症患者中。本研究旨在确定抗抑郁治疗后 SLC6A4 中的 DNA 甲基化是否发生变化，以及它是否影响抑郁症患者的治疗反应。总体而言，221 名韩国抑郁症患者完成了 6 周的选择性 5-羟色胺再摄取抑制剂（SSRI）单药治疗。治疗前和治疗后从静脉血中提取 DNA，并使用聚合酶链反应分析 DNA 甲基化。我们使用 Wilcoxon 的符号秩检验来验证治疗后甲基化的差异。使用汉密尔顿抑郁评定量表的 17 项评估治疗反应，定量 mRNA 水平。在调整了相关协变量后，SLC6A4 中特定 CpG 位点的 DNA 甲基化在治疗 6 周后发生了显著改变（CpG3、CpG4 和 CpG5 中的 p<0.001）。药物治疗后甲基化变化的幅度（ΔDNA 甲基化）与治疗反应或 mRNA 水平变化无关。SSRI 抗抑郁药可影响抑郁症患者的 SLC6A4 甲基化。然而，SLC6A4 中 CpG3、CpG4 和 CpG5 的 ΔDNA 甲基化与治疗反应无关。未来的研究应该探讨其他遗传变异和 CpG 甲基化对基因转录和抗抑郁治疗反应的综合影响。
