Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.
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We thank M. Schad, G. Ortega, and S. Jatzke for technical assistance, W. Davis and D. Drake for editorial assistance, and M. Altemus, J. Mizrahi, and A. Jaffe for logistical support. Supported by the Deutsche Forschungsgemeinschaft, the Bundesministerium für Bildung und Forschung, the European Commission, and the Intramural Research Programs of NIMH and NCI. K.P.L. is supported by the Hermann and Lilly Schilling Foundation
Volume 274 | Issue 5292
29 November 1996
29 November 1996
© 1996 American Association for the Advancement of Science.
Received: 13 June 1996
Accepted: 22 October 1996
Published in print: 29 November 1996
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