Dopamine transporter gene variant affecting expression in human brain is associated with bipolar disorder

Julia K. Pinsonneault, Dawn D. Han, Katherine E. Burdick, Maria Kataki, Alessandro Bertolino, Anil K. Malhotra, Howard H. Gu, Wolfgang Sadee

Research output: Contribution to journalArticlepeer-review


The gene encoding the dopamine transporter (DAT) has been implicated in CNS disorders, but the responsible polymorphisms remain uncertain. To search for regulatory polymorphisms, we measured allelic DAT mRNA expression in substantia nigra of human autopsy brain tissues, using two marker SNPs (rs6347 in exon 9 and rs27072 in the 3′-UTR). Allelic mRNA expression imbalance (AEI), an indicator of cis-acting regulatory polymorphisms, was observed in all tissues heterozygous for either of the two marker SNPs. SNP scanning of the DAT locus with AEI ratios as the phenotype, followed by in vitro molecular genetics studies, demonstrated that rs27072 CT affects mRNA expression and translation. Expression of the minor T allele was dynamically regulated in transfected cell cultures, possibly involving microRNA interactions. Both rs6347 and rs3836790 (intron8 5/6 VNTR) also seemed to affect DAT expression, but not the commonly tested 9/10 VNTR in the 3′UTR (rs28363170). All four polymorphisms (rs6347, intron8 5/6 VNTR, rs27072 and 3′UTR 9/10 VNTR) were genotyped in clinical cohorts, representing schizophrenia, bipolar disorder, depression, and controls. Only rs27072 was significantly associated with bipolar disorder (OR2.1, p0.03). This result was replicated in a second bipolar/control population (OR1.65, p0.01), supporting a critical role for DAT regulation in bipolar disorder.

Original languageEnglish
Pages (from-to)1644-1655
Number of pages12
Issue number8
Publication statusPublished - Jul 2011


  • allelic expression imbalance
  • bipolar disorder
  • dopamine transporter
  • rs27072
  • SLC6A3

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


Dive into the research topics of 'Dopamine transporter gene variant affecting expression in human brain is associated with bipolar disorder'. Together they form a unique fingerprint.

Cite this