Serotonin transporter: gene, genetic disorders, and pharmacogenetics.
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).
Murphy
Dennis L
DL
Laboratory of Clinical Science, Building 10, Room 3D41, 10 Center Drive, MSC 1264, NIMH, NIH, Bethesda, MD 20892, USA. murphyd@intra.nimh.nih.gov
Lerner
Alicja
A
Rudnick
Gary
G
Lesch
Klaus-Peter
KP
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
D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors