Correlation between serotonin uptake in human blood platelets with the 44-bp polymorphism and the 17-bp variable number of tandem repeat of the serotonin transporter
Correlation between serotonin uptake in human blood platelets with the 44-bp polymorphism and the 17-bp variable number of tandem repeat of the serotonin transporter
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DOI：
10.1002/ajmg.10119
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发表时间：
2002-04-08
期刊：
影响因子：
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通讯作者：
Brockmöller, J
中科院分区：
文献类型：
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作者：
Kaiser, R;Müller-Oerlinghausen, B;Brockmöller, J
中枢5-羟色胺（5-hydroxytryptamine，5-HT）系统的功能障碍似乎与精神疾病如精神分裂症或抑郁症有关。研究表明，5-HT转运蛋白（5-HTT）启动子区44 bp的插入/缺失多态性可能影响5-HTT基因的转录活性，该插入变异导致5-HTT表达和5-HT摄取增加。此外，第二内含子的17-bp可变数目串联重复序列（VNTR）多态性可以作为具有等位基因依赖性差异增强子样特性的转录调节因子。由于人血小板的5-HTT与神经组织的转运蛋白具有许多相同的性质，因此血小板被广泛用作替代组织来源，可能反映了中枢5-HT代谢。因此，我们调查了50名男性受试者的血小板中的44 bp多态性和17 bp VNTR的5-HT摄取的影响。我们发现44 bp多态性和17 bp VNTR对5-HT摄取的最大速率（V-max）没有显著影响。然而，具有17 bp VNTR的12个重复（STin2.12）的5-HTT内含子2等位基因的纯合个体似乎比STin2.10/STin2.9等位基因的杂合个体具有更低的5-HT摄取亲和力。这也被观察到的两个多态性的组合分析。总之，我们发现44 bp多态性和17 bp VNTR的不同基因型之间没有关联，5-HT摄取到血小板的最大速率。(C)2002 Wiley-Liss，Inc.
Dysfunctions of the central serotonin (5-hydroxytryrptamine, 5-HT) system seem to be associated with psychiatric disorders such as schizophrenia or depression. Previous studies suggested that a 44-bp insertion/deletion polymorphism of the 5-HT transporter (5-HTT) promoter region might influence the transcriptional activity of the 5-HTT gene, and the insertion variant resulted in increased 5-HTT expression and 5-HT uptake. Moreover, a 17-bp variable number of tandem repeat (VNTR) polymorphism of the second intron may act as a transcriptional regulator with allele dependent differential enhancer-like properties. Since the 5-HTT of human platelets shares many properties with the transporter of neural tissue, platelets are widely used as a surrogate tissue source, possibly reflecting central 5-HT metabolism. Therefore, we investigated the impact of the 44-bp polymorphism and the 17-bp VNTR for 5-HT uptake in platelets of 50 male subjects. We found no significant effect of the 44-bp polymorphism and of the 17-bp VNTR on maximum rate (V-max) of 5-HT uptake. However, individuals homozygous for the 5-HTT intron 2 allele with 12 repeats (STin2.12) of the 17-bp VNTR appeared to have lower affinity of 5-HT uptake than individuals heterozygous for the STin2.10/STin2.9 allele. This was also observed for the combined analysis of both polymorphisms. In conclusion, we found no association between the different genotypes of the 44-bp polymorphism and the 17-bp VNTR and maximum rate of 5-HT uptake into platelets. (C) 2002 Wiley-Liss, Inc.