Genetic polymorphisms of serotonin and dopamine transporters in mental disorders.
Transporter-assisted uptake of serotonin (5-HT) and dopamine (DA) has been accounted for activities in human behavior or mental status, because they are the sites of action of widely used antidepressant and psychoactive drugs. Both the human serotonin transporter (5-HTT) and human dopamine transporter (DAT1) genes are good candidates for etiological involvement in various psychiatric conditions. The serotonin transporter gene has two types of functional polymorphisms. One is serotonin transporter linked polymorphic region (5-HTTLPR) consisting of length variation of the repetitive sequence containing 20-23-bp-long repeat elements in the 5'-upstream region of the gene. Another polymorphism is that serotonin transporter variable number of tandem repeats (5-HTTVNTR) in its second intron. Both polymorphisms affect the transcription ratio of 5-HTT gene and may modify neuronal transmission by changing its protein expression. On the other hand, DAT1 gene has a variable number of tandem repeats type polymorphism (DAT1VNTR) in the 3'-untranslated region of the mRNA, which was also reported to change its gene expression. So polymorphic variations of transporters would change the behavioral and neuropathological tendency. Here, the feature of those two transporters and their relations to psychiatric disorders are described.
Ueno
Shu-ichi
S
Department of Psychiatry, The University of Tokushima School of Medicine, Tokushima, Japan.
D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000437:Alcoholism / Q000235:genetics; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D002648:Child; D003866:Depressive Disorder / Q000235:genetics; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D007438:Introns / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D001523:Mental Disorders / Q000235:genetics* / Q000378:metabolism; D018598:Minisatellite Repeats; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D012907:Smoking / Q000235:genetics; D009435:Synaptic Transmission; D014158:Transcription, Genetic
D020413:3' Untranslated Regions; D002352:Carrier Proteins; D004298:Dopamine; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493214:SLC6A3 protein, human; C493230:SLC6A4 protein, human