The silencer activity of the novel human serotonin transporter linked polymorphic regions

Enhancer/silencer activity of each allelic variant of the human serotonin transporter linked polymorphic region (5-HTTLPR) including newly found ones was measured in several cell lines including raphe-nucleus-derived RN46A. 5-HTTLR variants ligated in pGL-3 promoter vector increased luciferase activity in COS-7 cells and PC12 cells, where no significant differences among the variants were observed. In RN46 cell lines, however, 5-HTTLPRs decreased luciferase activity to 80-30%, acting as silencers not as enhancers. Some allelic variants (15, 19, 20 and 22) showed even significantly stronger silencer activities than others in RN46A. We also examined relationship between allelic frequencies, the enhancer/silencer activities and incidents of mood disorder. The categorized genotypic or allelic frequencies was not significantly different between the mood disorder and the control. No significant difference was detected either when analyzed by silencer activities of each allelic variant. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.