Human serotonin transporter gene (SLC6A4) variants: their contributions to understanding pharmacogenomic and other functional G×G and G×E differences in health and disease.
Human serotonin transporter gene (SLC6A4) variants: their contributions to understanding pharmacogenomic and other functional G×G and G×E differences in health and disease.
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DOI：
10.1016/j.coph.2011.02.008
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发表时间：
2011-02
影响因子：
4
通讯作者：
Moya, Pablo R.
中科院分区：
文献类型：
--
作者：
Murphy, Dennis L.;Moya, Pablo R.
最近在人类、啮齿动物和非人灵长类动物中对SLC 6A 4及其相应蛋白5-HT转运蛋白（SERT）的研究发现，SLC 6A 4非编码5′，3′ UTR和内含子区加上编码变体的组合在体外共同作用可使5-HT转运改变多达40倍。在体内，人和其他物种中的SLC 6A 4变体导致显著的生理变化，尽管减轻了5-HT受体的神经发育适应加上5-HT合成和代谢的补偿性改变。SLC 6A 4的多态性与情绪、内分泌和人格特征以及许多疾病的差异有关。该基因与基因x基因（G x G）和基因x环境（G x E）相互作用的组合仍然不完全清楚，一些关联研究结果仍然存在争议。考虑到其在整个多巴胺能系统的调节和功能中的首要重要性（如通过SRI如氟西汀在人类中的SERT介导的再摄取抑制以及小鼠和大鼠中的基因工程改变的结果所证明的），似乎SLC 6A 4和SERT将仍然是本领域试图更好地理解和治疗5-HT相关疾病的高度关注的领域。
Recent major findings from studies of SLC6A4 and its corresponding protein, the serotonin (5-HT) transporter (SERT) in humans, rodents and non-human primates indicate that combinations of SLC6A4 non-coding 5′, 3′ UTRs and intronic regions plus coding variants acting together can change 5HT transport as much as 40-fold in vitro. In vivo, SLC6A4 variants in humans and other species lead to marked physiological changes, despite mitigating neurodevelopmental adaptations in 5-HT receptors plus compensatory alterations in 5-HT synthesis and metabolism. Polymorphisms in SLC6A4 are associated with differences in emotional, endocrine, and personality characteristics as well as many diseases. This gene, in combinations with gene x gene (G x G) and gene x environment (G x E) interactions nonetheless remains incompletely understood, with some association findings remaining controversial. Considering its primary importance in the regulation and function of the entire serotonergic system (as evidenced by the consequences of SERT-mediated reuptake inhibition by SRIs like fluoxetine in humans and of genetically-engineered changes in mice and rats), it seems likely that SLC6A4 and SERT will remain areas of high interest in our field’s attempts to better understand and treat 5-HT-related disorders.
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影响因子：
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