title: Serotonin transporter: gene, genetic disorders, and pharmacogenetics.
abstract: The highly evolutionarily conserved serotonin transporter (SERT) regulates the entire serotoninergic system and its receptors via modulation 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 located. 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).
authors.affiliation: Laboratory of Clinical Science, Building 10, Room 3D41, 10 Center Drive, MSC 1264, NIMH, NIH, Bethesda, MD 20892, USA. murphyd@intra.nimh.nih.gov
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Murphy
authors.forename: Alicja
authors.initials: A
authors.lastname: Lerner
authors.forename: Gary
authors.initials: G
authors.lastname: Rudnick
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D019143:Evolution, Molecular; D030342:Genetic Diseases, Inborn; D020022:Genetic Predisposition to Disease; D006801:Humans; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D049268:Positron-Emission Tomography; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors