Iga Jun-Ichi, Watanabe Shin-Ya, Numata Shusuke, Umehara Hidehiro, Nishi Akira, Kinoshita Makoto, Inoshita Masatoshi, Shimodera Shinji, Fujita Hirokazu, Ohmori Tetsuro
Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Department of Neuropsychiatry, Kochi Medical School, Kochi University, Kochi, Japan.
Hum Psychopharmacol. 2016 May;31(3):193-9. doi: 10.1002/hup.2527. Epub 2016 Mar 23.
The serotonin transporter (5HTT) may be associated with the pathogenesis of major depressive disorder (MDD). The 5HTT-linked polymorphic region (5HTTLPR) genotype may determine how levels of 5HTT mRNA are influenced by promoter methylation. We examined the association of 5HTT gene methylation, which influences gene expression, and the 5HTTLPR genotype before antidepressant treatment and expression before and after treatment. The aims of this study were (1) to investigate the association between 5HTT methylation or expression in leukocytes and depression and (2) to investigate a possible effect of 5HTT methylation, expression, and genotype on clinical symptoms in MDD. The 5HTTLPR genotype was significantly associated with mean methylation levels in patients only (patients: r = 0.40, p = 0.035, controls: p = 0.96). The mean methylation level was significantly increased in patients compared with controls (patients: 5.30 ± 0.24, controls: 4.70 ± 0.19, unpaired t-test, p = 0.04). 5HTT expression using real-time PCR and Taqman probes was increased in unmedicated patients compared with controls and then decreased 8 weeks after antidepressant treatment. The mean 5HTT expression level was not associated with the 5HTTLPR genotype in patients or controls. Increased depressive symptoms were related to decreased levels of methylation. Copyright © 2016 John Wiley & Sons, Ltd.
血清素转运体（5HTT）可能与重度抑郁症（MDD）的发病机制有关。5HTT连锁多态性区域（5HTTLPR）基因型可能决定5HTT mRNA水平如何受启动子甲基化的影响。我们研究了影响基因表达的5HTT基因甲基化、抗抑郁治疗前的5HTTLPR基因型以及治疗前后的表达之间的关联。本研究的目的是：（1）调查白细胞中5HTT甲基化或表达与抑郁症之间的关联；（2）研究5HTT甲基化、表达和基因型对MDD临床症状的可能影响。5HTTLPR基因型仅在患者中与平均甲基化水平显著相关（患者：r = 0.40，p = 0.035，对照组：p = 0.96）。与对照组相比，患者的平均甲基化水平显著升高（患者：5.30±0.24，对照组：4.70±0.19，非配对t检验，p = 0.04）。与对照组相比，未用药患者使用实时PCR和Taqman探针检测的5HTT表达增加，抗抑郁治疗8周后降低。患者或对照组中5HTT平均表达水平与5HTTLPR基因型无关。抑郁症状加重与甲基化水平降低有关。版权所有©2016约翰威立父子有限公司。
