Sequence variation in the human dopamine transporter gene in subjects with bipolar disorder

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The dopamine (DA) transporter (hDAT, SLC6A3) plays a critical role in terminating synaptic DA neurotransmission and maintaining DA homeostasis. Dysfunction of hDAT is believed to contribute to various neuropsychiatric disorders such as attention deficit hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder (BPD). Recently, we identified a rare hDAT variant, Ala559Val, in two ADHD subjects, which has also been identified in a subject with BPD [Grunhage et al., 2000]. In this study, we are evaluating whether functional variants in hDAT exist in BPD and ascertain the transmission pattern and functional nature of identified polymorphisms. We utilize PCR and temperature‐gradient capillary electrophoresis (TGCE) to screen for mutations in the entire coding region and adjacent non‐coding sequence of the hDAT gene in a cohort of >400 BPD (Type 1 and II) subjects. Preliminary analyses reveal a number of both novel and common single nucleotide polymorphisms (SNPs) across the gene. Our study constitutes the largest analysis to date of DAT coding sequences in BPD, permitting the identification of both common and rare variants that could contribute to DAT dysfunction in the disorder. Supported by NIH grant #T32NS06120106 and T32MH064913; NIMH grant # MH073991, MH47612, MH59567, MH68503 and Veterans Affairs VISN 22 Mental Illness Research, Education, and Clinical Center.