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Exon and intron variants in the human tryptophan 2,3-dioxygenase gene: potential association with Tourette syndrome, substance abuse and other disorders

 

作者: David Comings,   Radhika Gade,   Donn Muhleman,   Connie Chiu,   Shijuan Wu,   Michael To,   Matthew Spence,   George Dietz,   Emily Winn-Deen,   Richard Rosenthal,   Henry Lesieur,   Loreen Rugle,   Jeffrey Sverd,   Linda Ferry,   James Johnson,   James MacMurray,  

 

期刊: Pharmacogenetics  (OVID Available online 1996)
卷期: Volume 6, issue 4  

页码: 307-318

 

ISSN:0960-314X

 

年代: 1996

 

出版商: OVID

 

关键词: oxygenase;tryptophan;serotonin;polymorphism;tryptophan 2,3 dioxygenase

 

数据来源: OVID

 

摘要:

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 JV-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-Tvariant 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 disorde.

 

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