Greenberg B D, Tolliver T J, Huang S J, Li Q, Bengel D, Murphy D L
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20892-1264, USA.
Am J Med Genet. 1999 Feb 5;88(1):83-7.
The human serotonin transporter (5-HTT), encoded by a single gene on chromosome 17q11.2, is expressed in brain and blood cells. 5-HTT is implicated in mood and anxiety regulation, and is where antidepressant and antianxiety drugs initially act in the brain. A 5-HTT-linked promoter region (5-HTTLPR) insertion/deletion polymorphism with long (l) and short (s) forms affects transporter expression and function. The s variant reduced 5-HTT gene transcription in a reporter gene construct and human lymphoblasts, resulting in reduced transporter levels and 5-HT uptake, acting as a dominant allele. In this study, we investigated the expression and function of 5-HTT in platelets from healthy male volunteers. The l variant was associated with more rapid initial platelet 5-HT uptake (Vmax), the index of platelet 5-HTT function most clearly heritable, while the s allele was dominant. The 5-HTTLPR genotype had no effect on platelet [3H]paroxetine binding (Bmax), affinity for [3H]5-HT or [3H]paroxetine, or 5-HT content. The 5-HT uptake findings support a functional difference in the two 5-HTTLPR variants, reinforcing their attractiveness as candidate genes in neuropsychiatric research.
人类血清素转运体（5-HTT）由位于17号染色体q11.2上的单个基因编码，在脑细胞和血细胞中表达。5-HTT与情绪和焦虑调节有关，是抗抑郁药和抗焦虑药在大脑中的初始作用位点。一种与5-HTT相关的启动子区域（5-HTTLPR）插入/缺失多态性，有长（l）和短（s）两种形式，会影响转运体的表达和功能。s变体在报告基因构建体和人类淋巴母细胞中降低了5-HTT基因转录，导致转运体水平和5-HT摄取减少，表现为显性等位基因。在本研究中，我们调查了健康男性志愿者血小板中5-HTT的表达和功能。l变体与更快的初始血小板5-HT摄取（Vmax）相关，Vmax是血小板5-HTT功能中最明显可遗传的指标，而s等位基因是显性的。5-HTTLPR基因型对血小板[3H]帕罗西汀结合（Bmax）、对[3H]5-HT或[3H]帕罗西汀的亲和力或5-HT含量没有影响。5-HT摄取的研究结果支持了两种5-HTTLPR变体在功能上的差异，增强了它们作为神经精神研究中候选基因的吸引力。
