title: Exon and intron variants in the human tryptophan 2,3-dioxygenase gene: potential association with Tourette syndrome, substance abuse and other disorders.
abstract: Defects in serotonin metabolism, and abnormalities in both blood serotonin and tryptophan levels, have been reported in many psychiatric disorders. Tryptophan 2,3-dioxygenase (TDO2) is the rate limiting enzyme for the breakdown of tryptophan to N-formyl kenurenine. Functional variants of this gene could account for the observed simultaneous increases or decreases of both serotonin and tryptophan in various disorders. We have identified four different polymorphisms of the human TDO2 gene. Association studies show a significant association of one or more of these polymorphisms and Tourette syndrome (TS), attention deficit hyperactivity disorder (ADHD) and drug dependence. The intron 6G-->T variant was significantly associated with platelet serotonin levels. Only the association with TS was significant with a Bonferroni correction (p = 0.005). Our purpose here is not to claim these associations are proven, but rather to report preliminary results and show that easily testable polymorphisms are available. We hope to encourage additional research into the potential role the TDO2 gene in these and other psychiatric disorders.
authors.affiliation: Department of medical Genetics, City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Comings
authors.forename: R
authors.initials: R
authors.lastname: Gade
authors.forename: D
authors.initials: D
authors.lastname: Muhleman
authors.forename: C
authors.initials: C
authors.lastname: Chiu
authors.forename: S
authors.initials: S
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: To
authors.forename: M
authors.initials: M
authors.lastname: Spence
authors.forename: G
authors.initials: G
authors.lastname: Dietz
authors.forename: E
authors.initials: E
authors.lastname: Winn-Deen
authors.forename: R J
authors.initials: RJ
authors.lastname: Rosenthal
authors.forename: H R
authors.initials: HR
authors.lastname: Lesieur
authors.forename: L
authors.initials: L
authors.lastname: Rugle
authors.forename: J
authors.initials: J
authors.lastname: Sverd
authors.forename: L
authors.initials: L
authors.lastname: Ferry
authors.forename: J P
authors.initials: JP
authors.lastname: Johnson
authors.forename: J P
authors.initials: JP
authors.lastname: MacMurray
mesh_terms: D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D006801:Humans; D007438:Introns; D011110:Polymorphism, Genetic; D012701:Serotonin / Q000097:blood; D019966:Substance-Related Disorders / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D005879:Tourette Syndrome / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D014364:Tryptophan / Q000097:blood; D014366:Tryptophan Oxygenase / Q000235:genetics*
chemical_list: D012701:Serotonin; D014364:Tryptophan; D014366:Tryptophan Oxygenase