Serotonin transporter (5-HTT) promoter genotype may influence the prolactin response to clomipramine
Serotonin transporter (5-HTT) promoter genotype may influence the prolactin response to clomipramine
复制标题
血清素转运蛋白 (5-HTT) 启动子基因型可能影响催乳素对氯米帕明的反应
作者：
R. Whale;D. Quested;D. Laver;Paul J. Harrison;P. Cowen
Abstract.Rationale:人5-羟色胺（5-HT）转运蛋白（5-HTT）基因启动子区的44个碱基对插入/缺失多态性产生被称为长（1）和短（s）的双等位基因多态性。s变体与5-HTT位点的较低表达和5-HT再摄取效率降低相关。目的：本研究的目的是确定急性5-HT再摄取阻断所产生的脑5-HT功能的增加是否受到5-HTT启动子l/s多态性的影响。研究方法：我们采用安慰剂对照的交叉设计，在14名健康女性受试者（7名ss基因型和7名ll基因型）中测量了急性给予三环类抗抑郁药氯丙咪嗪后血浆催乳素的增加，作为5-HT神经传递的指标。结果：氯丙咪嗪诱导催乳素释放与ll基因型的受试者显着更大。结论：我们的研究结果表明，急性5-羟色胺再摄取阻滞产生更大的增加5-羟色胺神经传递的受试者与ll基因型比那些与ss基因型。这些结果与临床数据一致，表明ss基因型受试者对选择性5-羟色胺再摄取抑制剂（SSRI）单药治疗的疗效较差。
Abstract.Rationale: A 44-base-pair insertion/deletion polymorphism in the promoter region of the human serotonin (5-HT) transporter (5-HTT) gene gives rise to a biallelic polymorphism designated long (l) and short (s). The s variant is associated with a lower expression of 5-HTT sites and a reduced efficiency of 5-HT reuptake. Objective: The aim of the present study was to determine whether the increase in brain 5-HT function produced by acute 5-HT reuptake blockade is influenced by the 5-HTT promoter l/s polymorphism. Methods: We measured the increase in plasma prolactin that follows acute administration of the tricyclic antidepressant clomipramine as an index of 5-HT neurotransmission in 14 healthy female subjects (7 with ss genotype and 7 with ll genotype) using a placebo-controlled crossover design. Results: Clomipramine-induced prolactin release was significantly greater in subjects with the ll genotype. Conclusion: Our findings suggest that acute 5-HT reuptake blockade produces a greater increase in 5-HT neurotransmission in subjects with the ll genotype than in those with an ss genotype. These results are consistent with clinical data indicating that subjects with an ss genotype may have a poorer therapeutic response to selective serotonin reuptake inhibitor (SSRI) monotherapy.