Differential serotonin transport is linked to the rh5-HTTLPR in peripheral blood cells.
Differential serotonin transport is linked to the rh5-HTTLPR in peripheral blood cells.
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差异5-羟色胺转运与外周血细胞中的RH5-HTTLPR有关。
DOI：
10.1038/tp.2012.2
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发表时间：
2012-02-07
影响因子：
6.8
通讯作者：
Andrews AM
中科院分区：
文献类型：
--
作者：
Singh YS;Altieri SC;Gilman TL;Michael HM;Tomlinson ID;Rosenthal SJ;Swain GM;Murphey-Corb MA;Ferrell RE;Andrews AM
人5-羟色胺转运体（SERT）基因具有43个碱基对（bp）的插入-缺失启动子多态性，即h5-HTTLPR。在许多研究中，该基因座的基因型与焦虑相关的人格特征和重度抑郁症风险的变化相关。然而，h5-HTTLPR与密切相关的单核苷酸多态性（SNP）结合的复杂作用仍有争议。此外，尽管SERT具有很高的临床意义，但体内转运蛋白功能仍然难以评估。恒河猴表达与h5-HTTLPR相关的启动子多态性。rh 5-HTTLPR与压力相关行为和认知灵活性的差异有关，尽管尚未研究5-羟色胺摄取的等位基因变异。我们研究了5-羟色胺系统，因为它涉及到5-HTTLPR在恒河猴外周血细胞。对rh 5-HTTLPR的测序显示了23-bp的插入，这比最初报道的要长一些。与以前的报告一致，在研究的个体中未检测到rh 5-HTTLPR和周围基因组区域的SNP。5-羟色胺摄取率、细胞表面SERT结合率和5-羟基吲哚乙酸/5-羟色胺比率的降低，但SERT mRNA水平的降低，与rh 5-HTTLPR短等位基因相关。因此，5-羟色胺摄取率与5-HTTLPR在容易接近的天然外周组织中是不同的。鉴于这些发现，我们预见，原代血细胞，结合高灵敏度的功能测量，使计时电流法，将是重要的研究改变与人类的遗传变异性和抗抑郁药的反应性5-羟色胺摄取。
The human serotonin transporter (SERT) gene possesses a 43-base pair (bp) insertion-deletion promoter polymorphism, the h5-HTTLPR. Genotype at this locus correlates with variation in anxiety-related personality traits and risk for major depressive disorder in many studies. Yet, the complex effects of the h5-HTTLPR, in combination with closely associated single-nucleotide polymorphisms (SNPs), continue to be debated. Moreover, although SERT is of high clinical significance, transporter function in vivo remains difficult to assess. Rhesus express a promoter polymorphism related to the h5-HTTLPR. The rh5-HTTLPR has been linked to differences in stress-related behavior and cognitive flexibility, although allelic variations in serotonin uptake have not been investigated. We studied the serotonin system as it relates to the 5-HTTLPR in rhesus peripheral blood cells. Sequencing of the rh5-HTTLPR revealed a 23-bp insertion, which is somewhat longer than originally reported. Consistent with previous reports, no SNPs in the rh5-HTTLPR and surrounding genomic regions were detected in the individuals studied. Reductions in serotonin uptake rates, cell surface SERT binding, and 5-hydroxyindoleacetic acid/serotonin ratios, but not SERT mRNA levels, were associated with the rh5-HTTLPR short allele. Thus, serotonin uptake rates are differentiable with respect to the 5-HTTLPR in an easily accessible native peripheral tissue. In light of these findings, we foresee that primary blood cells, in combination with high sensitivity functional measurements enabled by chronoamperometry, will be important for investigating alterations in serotonin uptake associated with genetic variability and antidepressant responsiveness in humans.
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影响因子：
11
作者：
通讯作者：
--
DOI：
10.1073/pnas.0800466105
发表时间：
2008-12-02
影响因子：
11.1
作者：
Baganz, Nicole L.;Horton, Rebecca E.;Daws, Lynette C.
通讯作者：
Daws, Lynette C.
影响因子：
4.3
作者：
Bartolomucci, Alessandro;Carola, Valeria;Gross, Cornelius
通讯作者：
Gross, Cornelius
DOI：
10.1097/01.alc.0000067976.62827.ed
发表时间：
2003-05-01
影响因子：
3.2
作者：
Barr, CS;Newman, TK;Higley, JD
通讯作者：
Higley, JD
影响因子：
7.6
作者：
Holmes, A;Yang, RJ;Crawley, JN
通讯作者：
Crawley, JN