Serotonin Transporter: Gene, Genetic Disorders, and Pharmacogenetics
- 1Laboratory of Clinical Science, Building 10, Room 3D41, 10 Center Drive, MSC 1264, NIMH, NIH, Bethesda, MD 20892;
- 2Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510;
- 3Molecular and Clinical Psychobiology, Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany
- Please address all correspondence to DLM. Email murphyd{at}intra.nimh.nih.gov; fax 301-402-0188.
Abstract
The highly evolutionarily conserved serotonin transporter (SERT) regulates the entire serotoninergic system and its receptors via mod-ulation of extracellular fluid serotonin concentrations. Differences in SERT expression and function produced by three SERT genes and their variants show associations with multiple human disorders. Screens of DNA from patients with autism, ADHD, bipolar disorder, and Tourette’s syndrome have detected signals in the chromosome 17q region where SERT is locat-ed. Parallel investigations of SERT knockout mice have uncovered multiple phenotypes that identify SERT as a candidate gene for additional human disorders ranging from irritable bowel syndrome to obesity. Replicated studies have demonstrated that the SERT 5′-flanking region polymorphism SS genotype is associated with poorer therapeutic responses and more frequent serious side effects during treatment with antidepressant SERT antagonists, namely, the serotonin reuptake inhibitors (SRIs).
- © American Society for Pharmacology and Experimental Theraputics 2004
