Genetic variation in the serotonin transporter promoter region affects serotonin uptake in human blood platelets

Benjamin D. Greenberg, Teresa J. Tolliver, Su Jan Huang, Qian Li, Dietmar Bengel, Dennis L. Murphy

Research output: Contribution to journalArticlepeer-review

467 Scopus citations


The human serotonin transporter (5-HTT), encoded by a single gene on chromosome 17q11.2, is expressed in brain and blood cells. 5-HTT is implicated in mood and anxiety regulation, and is where antidepressant and antianxiety drugs initially act in the brain. A 5-HTT-linked promoter region (5HTTLPR) insertion]deletion polymorphism with long (l) and short (s) forms affects transporter expression and function. The s variant reduced 5-HTT gene transcription in a reporter gene construct and human lymphoblasts, resulting in reduced transporter levels and 5-HT uptake, acting as a dominant allele. In this study, we investigated the expression and function of 5-HTT in platelets from healthy male volunteers. The I variant was associated with more rapid initial platelet 5-HT uptake (V(max)), the index of platelet 5- HTT function most clearly heritable, while the s allele was dominant. The 5- HTTLPR genotype had no effect on platelet [3H]paroxetine binding (B(max)), affinity for [3H]5-HT or [3H]paroxetine, or 5-HT content. The 5-HT uptake findings support a functional difference in the two 5-HTTLPR variants, reinforcing their attractiveness as candidate genes in neuropsychiatric research.

Original languageEnglish (US)
Pages (from-to)83-87
Number of pages5
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Issue number1
StatePublished - Feb 5 1999
Externally publishedYes


  • Genetic variants
  • Platelet serotonin uptake
  • Serotonin transporter promoter

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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