Dopaminergic polymorphisms in Tourette syndrome: Association with the DAT gene (SLC6A3)

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2007-07, Vol.144B (5), p.605-610
• Main Authors: Yoon, Dustin Y., Rippel, Christopher A., Kobets, Andrew J., Morris, Christina M., Lee, Jennifer E., Williams, Phillip N., Bridges, Dana D., Vandenbergh, David J., Shugart, Yin Y., Singer, Harvey S.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Alleles; association analyses; Attention Deficit Disorder with Hyperactivity - genetics; attention-deficit hyperactivity disorder; Biological and medical sciences; Child; Child, Preschool; DAT1 DdeI; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine beta-Hydroxylase - genetics; Dopamine Plasma Membrane Transport Proteins - genetics; Female; Genotype; Humans; Logistic Models; Male; Medical genetics; Medical sciences; Middle Aged; Neurology; Organic mental disorders. Neuropsychology; Polymorphism, Genetic; Protein Tyrosine Phosphatases - genetics; Proto-Oncogene Proteins - genetics; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Receptors, Dopamine - genetics; structural analysis; Tourette Syndrome - genetics
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.30466

Tourette syndrome (TS) is a chronic neuropsychiatric disorder characterized by involuntary motor and phonic tics. The pattern of inheritance and associated genetic abnormality has yet to be fully characterized. A dopaminergic abnormality in this disorder is supported by response to specific therapies, nuclear imaging, and postmortem studies. In this protocol, dopaminergic polymorphisms were examined for associations with TS and attention‐deficit hyperactivity disorder (ADHD). Polymorphisms investigated included the dopamine transporter (DAT1 DdeI and DAT1 VNTR), dopamine receptor (D4 Upstream Repeat and D4 VNTR), dopamine converting enzyme (dopamine β‐hydroxylase), and the acid phosphatase locus 1 (ACP1) gene. DNA was obtained from 266 TS individuals ± ADHD and 236 controls that were ethnicity‐matched. A significant association, using a genotype‐based association analysis, was identified for the TS‐total and TS‐only versus control groups for the DAT1 DdeI polymorphism (AG vs. AA, P = 0.004 and P = 0.01, respectively). Population structure, estimated by the genotyping of 27 informative SNP markers, identified 3 subgroups. A statistical re‐evaluation of the DAT1 DdeI polymorphism following population stratification confirmed the association for the TS‐total and TS‐only groups, but the degree of significance was reduced (P = 0.017 and P = 0.016, respectively). This study has identified a significant association between the presence of TS and a DAT polymorphism. Since abnormalities of the dopamine transporter have been hypothesized in the pathophysiology of TS, it is possible that this could be a functional allele associated with clinical expression. © 2006 Wiley‐Liss, Inc.