title: The DRD4 receptor Exon 3 VNTR and 5' SNP variants and mRNA expression in human post-mortem brain tissue.
abstract: Genetic variation within the dopamine D4 receptor (DRD4) gene has been implicated in many neuropsychiatric disorders and behavioral traits. This variation includes the extensively studied exon 3 variably numbered tandem repeat (VNTR), and several 5' polymorphisms including a120-bp duplication and two single-nucleotide polymorphisms at -521 C/T (rs1800955) and -616 C/G (rs747302). Several reports have provided evidence for a functional role for some of these variants using in vitro techniques. This study investigated the functionality of these polymorphisms in 28 human post-mortem brain tissue samples by quantifying DRD4 mRNA expression in relation to genotype. No statistically significant relationship between genotype and mRNA expression levels was found for these four polymorphisms although a weak trend toward the 7-repeat of the exon 3 VNTR reducing DRD4 mRNA expression was found. Employing post-mortem brain tissue, rather than using in vitro techniques may provide a more relevant paradigm to study functional effects of reported risk alleles.
authors.affiliation: Bute Medical School, University of St. Andrews, St. Andrews, Scotland, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Simpson
authors.forename: Glenn
authors.initials: G
authors.lastname: Vetuz
authors.forename: Mathew
authors.initials: M
authors.lastname: Wilson
authors.forename: Keeley J
authors.initials: KJ
authors.lastname: Brookes
authors.forename: Lindsey
authors.initials: L
authors.lastname: Kent
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001344:Autopsy; D001921:Brain / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D055815:Young Adult
chemical_list: C493599:DRD4 protein, human; D012333:RNA, Messenger; D050638:Receptors, Dopamine D4