Serotonin transporter protein (SLC6A4) allele and haplotype frequencies and linkage disequilibria in African- and European-American and Japanese populations and in alcohol-dependent subjects
Serotonin transporter protein (SLC6A4) allele and haplotype frequencies and linkage disequilibria in African- and European-American and Japanese populations and in alcohol-dependent subjects
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DOI：
10.1007/s004390050624
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发表时间：
1997-12-01
期刊：
影响因子：
5.3
通讯作者：
Cubells, JF
中科院分区：
文献类型：
--
作者：
Gelernter, J;Kranzler, H;Cubells, JF
SLC 6A 4基因座编码5-羟色胺转运蛋白，其反过来介导神经递质5-羟色胺的突触失活。已描述了该基因座的两种PCR格式多态性，第一种是位于外显子2的可变数量串联重复，第二种是位于启动子区的重复序列多态性。后一种多态性改变了SLC 6A 4的转录活性，并且据报道与焦虑和抑郁相关的性状有关。我们研究了等位基因频率，并计算单倍型频率和连锁不平衡措施，这两个多态性在欧洲，非洲裔美国人，日本人口，并在一组酒精依赖的欧洲-美国主题。两个系统的等位基因频率显示出变异，每个系统的总体差异显著，两个系统的每对群体之间的差异显著。群体间连锁不平衡也消失了。有没有显着差异的等位基因或单倍型频率之间的欧洲裔美国人的人口样本和酒精依赖的主题。在这些SLC 6A 4多态性的关联研究中，人群差异表明了人群分层的可能性。如果这个基因座的遗传变异真的与行为变异有关，那么这些结果可能反映了不同人群中不同的行为适应，或者是行为上重要但选择性中性的多态性的随机遗传漂变。
The SLC6A4 locus encodes the serotonin transporter, which in turn mediates the synaptic inactivation of the neurotransmitter serotonin. Two PCR-formatted polymorphisms at this locus have been described, the first of which is a variable number tandem repeat located in exon 2, and the second a repeat sequence polymorphism located in the promoter region. The latter polymorphism alters transcriptional activity of SLC6A4, and has been reported to be associated with anxiety and depression-related traits. We studied allele frequencies, and computed haplotype frequencies and linkage disequilibrium measures, for these two polymorphisms in European-American, African-American, and Japanese populations, and in a set of alcohol-dependent European-American subjects. Allele frequencies for both systems showed variation, with significant differences overall for each system, and significant differences between each pair of populations for both systems. Linkage disequilibrium also vaned among the populations. There were no significant differences in allele or haplotype frequencies between the European American population samples and alcohol-dependent subjects. The population differences demonstrate a potential for population stratification in association studies of either of these SLC6A4 polymorphisms. If genetic variation at this locus really is associated with behavioral variation, these results could reflect either different behavioral adaptations in different populations, or random genetic drift of a behaviorally important but selectively neutral polymorphism.