Suicide attempts and the tryptophan hydroxylase gene (original) (raw)

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme of serotonin synthesis. In this casecontrol 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 ( 2 = 11.2, df = 1, P Ͻ 0.0008 for the allele distribution; these loci are in complete linkage disequilibrium) and in the 3Ј noncoding region ( 2 = 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 3Ј part of the TPH gene may be a susceptibility factor for a phenotype combining suicidal behavior, mood disorder and impulsive aggression. Molecular Psychiatry (2001) 6, 268-273.