NO EVIDENCE OF LINKAGE OR ASSOCIATION BETWEEN TYROSINE-HYDROXYLASE GENE AND AFFECTIVE-DISORDER

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of dopamine and norepinephrine, and therefore is of significant interest as a candidate gene in studies of affective disorders. We have carried out the linkage study between the susceptibility gene for affective disorder and tetranucleotide polymorphism of TH gene in five Japanese pedigrees. In addition to the linkage approach, we have undertaken an allelic association study using 74 patients with affective disorder and 78 controls with polymorphisms at the TH gene and the nearby dopamine D4 receptor gene. No evidence for linkage or associations were found. These results indicate that TH gene is less likely to contribute to the genetic component of affective disorders.