Article

Variability of the tryptophan hydroxylase gene: Study in victims of violent suicide

University of Zagreb, Zagrabia, Grad Zagreb, Croatia
Psychiatry Research (Impact Factor: 2.68). 04/2005; 134(1):67-73. DOI: 10.1016/j.psychres.2004.04.011
Source: PubMed

ABSTRACT Tryptophan hydroxylase (TPH), the enzyme controlling serotonin synthesis, is considered to be a potential contributor to the biological substrate of suicide. The association of the promoter (-7065CT) and intron 7 (218AC) polymorphisms, and the related haplotype, of the Tph1 gene with suicidal behavior was investigated in a sample of 160 victims of violent suicide and 284 healthy controls. All individuals were males of Croatian (Slavic) origin. Allele frequencies of both polymorphisms in Croatian controls were similar to control values reported for other European populations. Alleles at the two loci demonstrated highly significant linkage disequilibrium. No differences between controls and victims for the Tph1 genetic variation, either at single loci, or at a haplotypic level, were demonstrated, albeit there was a tendency, not reaching statistical significance, towards an increase of the intron 7CC genotype in the suicide group. Negative association results on the individual Tph1 loci, in accordance with the majority of previous reports, confirmed the lack of their major effect also in the Slavic ethnicity. Haplotypic results, on the other hand, opposing the previous positive finding, point to the possible influence of ethnicity (or gender) on the association between the Tph1 gene polymorphism and suicide.

Download full-text

Full-text

Available from: Jasminka Stefulj, Nov 20, 2014
0 Followers
 · 
69 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: INTRODUCTION: Strong evidence demonstrates a genetic susceptibility to suicidal behaviour and a relationship between suicide and mental disorders. The aim of this study was to test for association between suicide and five selected genetic variants, which had shown association with suicide in other populations. METHOD: We performed a nationwide case-control study on all suicide cases sent for autopsy in Denmark between the years 2000 and 2007. The study comprised 572 cases and 1049 controls and is one of the largest genetic studies in completed suicide to date. The analysed markers were located within the Serotonin Transporter (SLC6A4), Monoamine Oxidase-A (MAOA) and the Tryptophan Hydroxylase I and II (TPH1 and TPH2) genes. RESULTS: None of the genetic markers within SLC6A4, MAOA, TPH1 and TPH2 were significantly associated with completed suicide or suicide method in the basic association tests. Exploratory interaction test showed that the minor allele of rs1800532 in TPH1 has a protective effect for males younger than 35 years and females older than 50 years, whereas for the oldest male subjects, it tended to be a risk factor. We also observed a significant interaction between age-group and the 5-HTTLPR genotype (with and without rs25531) in SLC6A4. The long allele or high expression allele tends to have a protective effect in the middle age-group. LIMITATION: We only analysed a limited number of genetic variants. CONCLUSION: None of the analysed variants are strong risk factors. To reveal a better understanding of the genes involved in suicide, we suggest future studies should include both genetic and non-genetic factors.
    Journal of Affective Disorders 01/2013; 148(2-3). DOI:10.1016/j.jad.2012.12.011 · 3.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Untersuchung zu single-nucleotid-polymorphismen (SNPs) der Serotoninrezeptoren 5-HT2A, 5-HT3A, des Neurotrophins BDNF und des Enzyms Tryptophanhydroxlase auf deren Korrelation mit Migräne mit und ohne Aura. Correlation between single nucleotide polymorphisms in genes of serotonergic 5-HT2A and 5-HT3A-receptors, brain derived neurotropic factor and Tryptophanhydroxylase with migraine with and without aura phenomenon.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Serotonin is a widely investigated neurotransmitter in several psychopathologies, including suicidal behavior (SB); however, its role extends to several physiological functions involving the nervous system, as well as the gastrointestinal and cardiovascular systems. This review summarizes recent research into ten serotonergic genes related to SB. These genes - TPH1, TPH2, SLC6A4, SLC18A2, HTR1A, HTR1B, HTR2A, DDC, MAOA, and MAOB - encode proteins that are vital to serotonergic function: tryptophan hydroxylase; the serotonin transporter 5-HTT; the vesicular transporter VMAT2; the HTR1A, HTR1B, and HTR2A receptors; the L-amino acid decarboxylase; and the monoamine oxidases. This review employed a systematic search strategy and a narrative research methodology to disseminate the current literature investigating the link between SB and serotonin.
    Neuropsychiatric Disease and Treatment 11/2013; 9:1699-1716. DOI:10.2147/NDT.S50300 · 2.15 Impact Factor