Tryptophan hydroxylase (TPH) is the rate-limiting enzyme of serotonin synthesis. In this case-control study, we investigated whether the TPH gene was a susceptibility factor for suicidal behavior. Seven polymorphisms spanning the entire gene were studied in a case-control study including 231 individuals who had attempted suicide and 281 controls. Significant associations were found between variants in introns 7, 8 and 9 (χ2 = 11.2, df = 1, P < 0.0008 for the allele distribution; these loci are in complete linkage disequilibrium) and in the 3′ non-coding region (χ2 = 30.94, P = 0.0014) and suicide attempt. The association was strongest for subjects who had attempted suicide by violent means and who had a history of major depression. No significant association was observed between suicide attempts and polymorphisms in the promoter, intron 1 and intron 3. The results presented here, and those of previous studies, suggest that a genetic variant of the 3′ part of the TPH gene may be a susceptibility factor for a phenotype combining suicidal behavior, mood disorder and impulsive aggression.
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Abbar, M., Courtet, P., Bellivier, F., Leboyer, M., Boulenger, J. P., Castelhau, D., … Buresi, C. (2001). Suicide attempts and the tryptophan hydroxylase gene. Molecular Psychiatry, 6(3), 268–273. https://doi.org/10.1038/sj.mp.4000846