Background
Several polymorphisms have been identified in the 5′flanking region of the human dopamine
D4 receptor gene (DRD4), including a tandem duplication polymorphism. This comprises
a 120-base-pair repeat sequence that is known to have different allele frequencies
in various populations around the world. Furthermore, various studies have revealed
evidence of linkage to attention-deficit/hyperactivity disorder and association with
schizophrenia and methamphetamine abuse. The location of the polymorphism in the 5′regulatory
region of the DRD4 gene and the fact that it consists of potential transcription factor
binding sites suggest that it might confer differential transcriptional activity of
the alleles.
Methods
We investigated the functional effects of this gene variant with transient transfection
methods in four human cell lines and then assessed transcriptional activity with luciferase
reporter gene assays.
Results
The longer allele has lower transcriptional activity than the shorter allele in SK-N-MC,
SH-SY5Y, HEK293, and HeLa cell lines.
Conclusions
This evidence suggests that the duplication might have a role in regulating the expression
of the DRD4 gene and provides an understanding of the biological mechanisms underlying
the etiology of neuropsychiatric disorders such as ADHD, schizophrenia, and metamphetamine
abuse.
Keywords
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Article info
Publication history
Accepted:
August 25,
2004
Received in revised form:
July 20,
2004
Received:
February 26,
2004
Identification
Copyright
© 2004 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
