Suicide attempts and the tryptophan hydroxylase gene.
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 (chi(2) = 11.2, df = 1, P< 0.0008 for the allele distribution; these loci are in complete linkage disequilibrium) and in the 3' noncoding region (chi(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 3' part of the TPH gene may be a susceptibility factor for a phenotype combining suicidal behavior, mood disorder and impulsive aggression.
Abbar
M
M
Department of Psychiatry, Carémeau Hospital, Nîmes, France.
Courtet
P
P
Bellivier
F
F
Leboyer
M
M
Boulenger
J P
JP
Castelhau
D
D
Ferreira
M
M
Lambercy
C
C
Mouthon
D
D
Paoloni-Giacobino
A
A
Vessaz
M
M
Malafosse
A
A
Buresi
C
C
D000328:Adult; D001923:Brain Chemistry / Q000235:genetics*; D016022:Case-Control Studies; D003863:Depression / Q000235:genetics; D005260:Female; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012701:Serotonin / Q000378:metabolism; D013406:Suicide, Attempted; D014365:Tryptophan Hydroxylase / Q000235:genetics* / Q000378:metabolism; D014754:Violence
D012701:Serotonin; D014365:Tryptophan Hydroxylase