Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region.
Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.
Lesch
K P
KP
Department of Psychiatry, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany. kplesch@rzbox.uni-wuerzburg.de
Bengel
D
D
Heils
A
A
Sabol
S Z
SZ
Greenberg
B D
BD
Petri
S
S
Benjamin
J
J
Müller
C R
CR
Hamer
D H
DH
Murphy
D L
DL
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001008:Anxiety Disorders / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009497:Neurotic Disorders / Q000235:genetics*; D009679:Nuclear Family; D010556:Personality Tests; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D014162:Transfection
D002352:Carrier Proteins; D005819:Genetic Markers; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin