Tryptophan hydroxylase gene 218A/C polymorphism is not associated with depressed suicide.

Abstract

Abnormalities in functioning of the central serotonergic system are believed to be involved in the pathogenesis of depressive illness and suicidal behaviour. Recently, polymorphism in the tryptophan hydroxylase (TPH) gene has been studied for association with aggression, anger-related traits and suicidal behaviour, but the results are inconclusive. The present investigation was to determine whether there are differences in genotype and allele distribution of the TPH gene 218A/C polymorphism in post-mortem brain samples from 35 depressed suicide victims and 84 control subjects of the same ethnic background. A functional polymorphism in the promoter region of 5-HT transporter gene was also re-examined in this increased sample size. No significant difference in TPH gene 218A/C polymorphism between controls and depressed suicide victims was detected. This may suggest that the TPH gene has no significant effect on suicidality in depressed subjects. In a previous study on a smaller sample we found the frequency of the long allele of 5-HT transporter gene to be higher in depressed suicide victims. In this increased sample size, both the genotype and alleles of the 5-HT transporter gene were significantly associated with completed suicide. The frequency of the L/L genotype in depressed suicide victims was almost double of that found in control group (48.6 vs. 26.2%). The odds ratio for the L allele associated with depressed suicide was 2.1 (95% CI, 1.2-3.7). The relatively small sample size does not exclude the possibility of false-positive results and the finding needs replication.