Suicide attempts and the tryptophan hydroxylase gene

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme of serotonin synth esis. 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 individ uals who had attempted suicide and 281 controls. Significant associations w ere found between variants in introns 7, 8 and 9 (chi (2) = 11.2, df = 1, P <0.0008 for the allele distribution; these loci are in complete linkage dis equilibrium) and in the 3' noncoding region (<chi>(2) = 30.94, P= 0.0014) a nd suicide attempt. The association was strongest for subjects who had atte mpted suicide by violent means and who had a history of major depression. N o significant association was observed between suicide attempts and polymor phisms 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' par t of the TPH gene may be a susceptibility factor for a phenotype combining suicidal behavior, mood disorder and impulsive aggression.