Molecular genetics of monoamine transporters: relevance to brain disorders

Abstract

We have demonstrated in both the human serotonin transporter gene (5HTT) and the dopamine transporter gene (DAT1) that specific polymorphic variants termed Variable Number Tandem Repeats (VNTRs), which correlate with predisposition to a number of neurological and psychiatric disorders, act as transcriptional regulatory domains. We have demonstrated that these domains can act as both tissue-specific and stimulus-inducible regulators of gene expression. As such they can act to be mechanistically associated with the progression or initiation of a behavioural disorder by altering the level of transporter mRNA, which in turn regulates the concentration of transporter in specific cells or in response to a challenge; chemical, environmental or physiological. The synergistic actions of such transcriptional domains will modulate gene expression. Our hypothesis is that these VNTR variants are one mechanism by which nurture can modify concentrations of neurotransmitters in a differential manner.