No significant differences were found in TPH protein level or 5HT2A receptor density between suicide victims and controls. There was a significant negative correlation, however, between TPH protein level and 5HT2A receptor density. The variation of the TPH gene (the A218C polymorphism: a single base transition, A to C) had a significant influence on both TPH protein level and 5HT2A receptor binding. The AA genotype of the A218C polymorphism of the TPH gene showed higher TPH protein level along with lower 5HT2A receptor density than did any other genotypes in the postmortem brains of both suicide victims and controls.
The major finding of the study was that the A218C polymorphism of the TPH gene altered TPH protein level in postmortem brain samples from both those who did commit suicide and those who did not. There was no change in TPH protein level or 5HT2A receptor density in the postmortem brain of the suicide victims, compared to the controls. These results together suggest that the A218C polymorphism of the TPH gene does not play a major role in the biological suicidality, but seems to be involved in the serotonergic function. In conclusion, the findings suggest that the genetic variation of the A218C polymorphism of the TPH gene is likely to affect the regulation of TPH expression. This may provide new insights not only for the biological studies of suicide but also for research into the behavioral characteristics that may be associated with serotonergic dysfunction.
Citation source: Molecular Psychiatry 2002 Volume 7, number 10, pages 1127-1132.
For further information on this work, please contact Dr. Osamu Shirakawa, Division of Psychiatry and Neurology, Department of Environmental Health and Safety, Faculty of Medical Sciences, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho Chuo-Ku, Kobe 650-0017, Japan. Phone: 81-78-382-6065, Fax: 81-78-382-6079, E-mail: sirakawa@kobe-u.ac.jp
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