Expression of the dopamine transporter gene is regulated by the 3' UTR VNTR: Evidence from brain and lymphocytes using quantitative RT-PCR.
Genetic association studies provide considerable evidence that the 10-repeat allele of a variable number tandem repeat (VNTR) in the 3'-untranslated region (3'-UTR) of the dopamine transporter gene (DAT1) is associated with a range of psychiatric phenotypes, most notably, attention deficit hyperactivity disorder. The mechanism for this association is not yet understood, although several lines of evidence implicate variation in gene expression. In this study, we measured DAT1 messenger RNA levels in cerebellum, temporal lobe, and lymphocytes using quantitative real-time reverse-transcription polymerase chain reaction. Relative to a set of four control housekeeping genes (beta-actin, GAPD, ribosomal 18S, and beta2-microglobulin) we observed that increased levels of DAT1 expression were associated with the number of 10-repeat alleles. These data provide direct evidence that the VNTR, or another polymorphism in linkage disequilibrium with the VNTR, is involved in regulating expression of this gene.
Mill
Jonathan
J
Social, Genetic, and Developmental Research Centre, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, United Kingdom. j.mill@iop.kcl.ac.uk
Asherson
Philip
P
Browes
Clare
C
D'Souza
Ursula
U
Craig
Ian
I
D020413:3' Untranslated Regions; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D001921:Brain / Q000502:physiology; D050483:Dopamine Plasma Membrane Transport Proteins; D005786:Gene Expression Regulation; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000235:genetics*; D018598:Minisatellite Repeats; D009419:Nerve Tissue Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020413:3' Untranslated Regions; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human