Murphy Dennis L, Lerner Alicja, Rudnick Gary, Lesch Klaus-Peter
Laboratory of Clinical Science, Building 10, Room 3D41, 10 Center Drive, MSC 1264, NIMH, NIH, Bethesda, MD 20892, USA.
Mol Interv. 2004 Apr;4(2):109-23. doi: 10.1124/mi.4.2.8.
The highly evolutionarily conserved serotonin transporter (SERT) regulates the entire serotoninergic system and its receptors via modulation of extracellular fluid serotonin concentrations. Differences in SERT expression and function produced by three SERT genes and their variants show associations with multiple human disorders. Screens of DNA from patients with autism, ADHD, bipolar disorder, and Tourette's syndrome have detected signals in the chromosome 17q region where SERT is located. Parallel investigations of SERT knockout mice have uncovered multiple phenotypes that identify SERT as a candidate gene for additional human disorders ranging from irritable bowel syndrome to obesity. Replicated studies have demonstrated that the SERT 5'-flanking region polymorphism SS genotype is associated with poorer therapeutic responses and more frequent serious side effects during treatment with antidepressant SERT antagonists, namely, the serotonin reuptake inhibitors (SRIs).
高度进化保守的血清素转运体（SERT）通过调节细胞外液血清素浓度来调控整个血清素能系统及其受体。三个SERT基因及其变体所产生的SERT表达和功能差异与多种人类疾病相关。对自闭症、注意力缺陷多动障碍、双相情感障碍和妥瑞氏综合征患者的DNA筛查在SERT所在的17q染色体区域检测到了信号。对SERT基因敲除小鼠的平行研究发现了多种表型，这些表型将SERT确定为从肠易激综合征到肥胖症等更多人类疾病的候选基因。重复研究表明，SERT 5'侧翼区域多态性SS基因型与使用抗抑郁SERT拮抗剂（即血清素再摄取抑制剂，SRIs）治疗期间较差的治疗反应和更频繁的严重副作用相关。
