Intronic polymorphism of tryptophan hydroxylase and serotonin transporter: indication for combined effect in predisposition to suicide.
Indices of disturbed serotonergic neurotransmission are the most robust biological findings in suicide. Tryptophan hydroxylase (TPH) and 5-hydroxytryptamine transporter (5HTt) are the main regulators of 5HT signaling. Owing to the assumed functionality of intronic polymorphisms of TPH (218AC) and 5HTt (VNTR-2) genes, we investigated frequencies of concurrence of the TPH and 5HTt genotypes containing "lower activity" alleles (CC and 1010, respectively), in 192 suicide victims and 377 controls. Significant differences in frequencies of 5HTt and TPH genotype combinations were found between suicide victims and control subjects (p = 0.0156), with a clear dose-effect of the suspected ("lower activity") genotypes (p = 0.0046). Concurrent presence of the two, allegedly transcriptionally less active, variants of these genes seems to be in some kind of relation to the increased susceptibility to suicide.
Jernej
B
B
Laboratory of Neurochemistry and Molecular Neurobiology, Rudjer Boskovic Institute, Zagreb, Croatia. jernej@rudjer.irb.hr
Stefulj
J
J
Hranilovic
D
D
Balija
M
M
Skavic
J
J
Kubat
M
M
D002352:Carrier Proteins / Q000235:genetics*; D017523:Croatia; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins; D013405:Suicide / Q000208:ethnology; D014365:Tryptophan Hydroxylase / Q000235:genetics*
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D014365:Tryptophan Hydroxylase