Norepinephrine transporter polymorphisms in Tourette syndrome with and without attention deficit hyperactivity disorder: no evidence for significant association.

Noradrenergic abnormalities have been proposed in the pathophysiology of Tourette syndrome and attention-deficit hyperactivity disorder. Patients with Tourette syndrome with (n=115) and without (n=110) attention-deficit hyperactivity disorder were evaluated for association with two single nucleotide polymorphisms of the norepinephrine transporter gene (SLC6A2); a T-182C single nucleotide polymorphism located in the 5' flanking promoter region and a silent mutation (G1287A) occurring in exon 9. A polymerase chain reaction restriction enzyme assay was developed for the T-182C single nucleotide polymorphism based on a prior sequencing methodology. In this case-control study, no association was identified between either polymorphism and Tourette syndrome or attention-deficit hyperactivity disorder. In a small subset, these NET polymorphisms did not predict therapeutic response to the noradrenergic transporter inhibitor atomoxetine. Further research with additional NET polymorphisms and larger sample sizes are indicated in the pursuit of biomarkers for therapeutic responders.