Membrane Transporters in Drug Discovery and Development

Volume 637 of the series Methods in Molecular Biology pp 165-180


Genetic Variants in the Vesicular Monoamine Transporter 1 (VMAT1/SLC18A1) and Neuropsychiatric Disorders

  • Falk W. LohoffAffiliated withTranslational Research Laboratories, Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine

* Final gross prices may vary according to local VAT.

Get Access


Vesicular monoamine transporters (VMATs) are involved in the presynaptic packaging of monoaminergic neurotransmitters into storage granules. Upon an action potential, vesicles release their contents into the synaptic cleft via exocytosis. Since insufficient or excess release of neurotransmitter might alter neurochemical function and neurotransmission, VMATs are an important target for biological research in neuropsychiatric disorders. Two structurally related but pharmacologically distinct VMATs have been identified, encoded by separate genes, VMAT1 (SLC18A1) and VMAT2 (SLC18A2). Although it was reported initially that only VMAT2 is expressed in brain, recent studies indicate that VMAT1 is also expressed in brain, thus making both transporters plausible candidate genes for neuropsychiatric disorders. The gene encoding VMAT1 is located on chromosome 8p21, a region implicated in linkage studies of schizophrenia, bipolar disorder, and anxiety-related phenotypes. Furthermore, several recent genetic case–control studies have documented an association between common missense variations in the VMAT1 gene and susceptibility to bipolar disorder and schizophrenia. Variations in the VMAT1 gene might affect transporter function and might be involved in the etiology of neuropsychiatric disorders. This chapter describes methods for genotyping three missense polymorphisms implicated in neuropsychiatric disorders (Thr4Pro, Thr98Ser, Thr136Ile) using TaqMan-based PCR and standard PCR approaches.

Key words

Vesicular monoamine transporter psychiatric disorders schizophrenia bipolar disorder depression genetics brain expression reserpine tetrabenazine SLC18A1