TPH gene polymorphism and aging: Indication of combined effect on the predisposition to violent suicide

Abstract

Findings relating serotonin to suicidal behavior suggest the role of genes for tryptophan hydroxylase (TPH) in the genetic substrate of this disorder. Association of Tph1 gene and suicidality, despite considerable research efforts, remains controversial. Polymorphism A218C in intron 7 of Tph1 gene was studied in violent suicide victims (N = 247) and controls (N = 320) of Slavic (Croatian) origin, with specific consideration of the influence of subjects' age. The frequency of, allegedly less active, CC genotype was increased in older (above 65 years) victims as compared to controls (P = 0.0126 and 0.0008, for comparison with age-specific and integral control samples, respectively), while there were no differences between victims under 65 years and controls. Excess of the CC genotype in elderly victims of violent suicide points to the possible combined effect of the respective genetic factor and physiological changes during aging on the predisposition to this disorder.

Genetic Association Studies of Suicidal Behavior: A Review of the Past 10 Years, Progress, Limitations, and Future Directions

“…On a clinical level, it is interesting to note that in the Galfalvy et al ( 41 ) study, intron 7 genotype AA was associated with both fewer reasons for living and greater impulsivity. Regarding the C allele (A218C), only the study by Stefulj et al ( 39 ) shows an association with SB just in people aged over 65 years. However, the association is relatively weak, the number of subjects aged over 65 years is limited ( n = 74), and the medical records of those who died could not all be obtained.…”

Exploring epistasis in candidate genes for antisocial personality disorder

“…TPH1 involves an important role of intron 7 (rs1800532) (Tables 2 and 3). TPH catalyzes the biopterin-dependent monooxygenation of tryptophan to 5-hydroxytryptophan; therefore, it is critical in the fine tuning of serotonergic neurotransmission (Stefulj et al, 2006). Recently, Nielsen et al (1994) had hypothesized that variants in the TPH1 gene was found to be associated with the concentration of cerebrospinal fluid-5-hydroxy indolacetic acid (CSF-5-HIAA-) in violent behaviors; remarkably, the tightly linked rs1800532 TPH1 variant was reported with comorbid disorders associated with ASPD such as alcoholism and drug addiction (Nielsen et al, 1994(Nielsen et al, , 2008Hill et al, 2002;Chung et al, 2005).…”

Functional promoter polymorphism of the neuronal isoform of tryptophan hydroxylase (Tph2) in suicide

“…Our earlier research has also given some support to this concept (Hranilovic et al, 2003;Jernej et al, 2004;Stefulj et al, 2006). Therefore, association studies on genes encoding synaptic proteins of this transmitter, including recently discovered Tph2, should be encouraged, with negative reports being as important as positive ones in obtaining realistic picture of true genetic influences.…”