TPH1 A218 allele is associated with suicidal behavior in Turkish population

Beden, Onur; Şenol, Ender; Atay, Sevcan; Ak, Handan; Altıntoprak, Ayşe Ender; Kiyan, Güçlü Selahattin; Petin, Buket; Yaman, Utku; Aydin, Hikmet Hakan

doi:10.1016/j.legalmed.2016.05.005

Cited by 16 publications

(18 citation statements)

References 35 publications

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“…Similarly, in the case of the TPH1 polymorphism, we confirmed that the A/A genotype increased the risk of stroke. Moreover, the frequency of A allele was high in suicide attempters as compared to healthy volunteers in a Turkish population [32]. However, the same polymorphism was not associated with the occurrence of schizophrenia in Japanese populations [33].…”

Section: Discussionmentioning

confidence: 85%

Variation of Genes Encoding Tryptophan Catabolites Pathway Enzymes in Stroke

Wigner

Saluk‐Bijak

Synowiec

et al. 2019

JCM

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The abnormal activation of the tryptophan catabolites pathway (TRYCATs) is observed in patients suffering from cerebrovascular disease, including stroke. A previous study confirmed that lower bioavailability of tryptophan for serotonin synthesis was characterized in the patients during the acute stroke phase. Interestingly, according to various studies, polymorphisms of the genes involved in the TRYCATs pathway may modulate the risk of stroke occurrence. Therefore, this study aimed to investigate the association between the occurrence of TPH1, TPH2, KAT1, KAT2 and IDO1 polymorphisms and the risk of stroke development.The following 10 polymorphisms of the genes encoding enzymes of the TRYCATs pathway were selected: c.804-7C > A (rs10488682), c.-1668T > A (rs623580), c.803+221C > A (rs1800532), c.-173A > T (rs1799913) – TPH1, c.-1449C > A (rs7963803), and c.-844G > T (rs4570625) – TPH2. c.*456G > A of KAT1 (rs10988134), c.975-7T > C of KAT2 (rs1480544), c.-1849C > A (rs3824259) and c. -1493G > C (rs10089084) of IDO1. The study was carried out on DNA isolated from the peripheral blood taken from 107 patients after a stroke and 107 healthy volunteers. All DNA samples were genotyped using TaqMan probes. The genotypes of eight studied polymorphisms modulated the risk of stroke. No significant difference in genotype and allele frequencies of the c.804-7C > A –TPH1 (rs10488682) and c.*456G > A – KAT1 (rs10988134) polymorphisms were found between patients and controls. Having performed haplotype and gen-gen analyses, it was possible to determine that patients after a stroke and controls differed in terms of the frequency of selected genotypes and haplotypes. Among the studied polymorphisms, eight SNPs were linked with stroke risk modulation. The results obtained confirmed our hypothesis regarding the involvement of the TRYCATs pathway in the pathogenesis of stroke.

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Section: Discussionmentioning

confidence: 85%

Variation of Genes Encoding Tryptophan Catabolites Pathway Enzymes in Stroke

Wigner

Saluk‐Bijak

Synowiec

et al. 2019

JCM

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“…There is a strong relationship between SB and A779C / A218C polymorphisms in both European and Asian populations (Mirkovic et al 2016). The prevalence of TPH1 A218C polymorphism was evaluated in a Turkish population and a significant relationship was found between the A allele and SB (Beden et al 2016). It was shown that not only the AA genotype but also the CC genotype was significantly associated with suicide risk and depression (Zalsman et al 2001).…”

Section: Suicidal Behavior (Sb)mentioning

confidence: 99%

“…A multi-center case-control study and meta-analysis showed that the A218/A779 locus increased sensitivity to schizophrenia and contributed to psychiatric disorders characterized by high suicide rates rather than affecting suicide (Beden et al 2016). Although it was not associated with SB, there was a significant relationship between bipolar disorder (BPD) and small alleles of A218C in individuals with psychiatric disorders (Beden et al 2016).…”

Section: Suicidal Behavior (Sb)mentioning

confidence: 99%

TPH1 (tryptophan hydroxylase 1)

Gurbanov¹,

Karaçam²

2020

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Tryptophan hydroxylase 1 gene (TPH1) encodes a rate-limiting enzyme in the biosynthesis of the monoamine neurotransmitter serotonin. TPH1 is expressed in peripheral tissues such as the heart, lung, kidney, duodenum and adrenal gland, as well as in female reproductive tissues. The mutations in this gene have been associated with various diseases with high risk, including, schizophrenia, somatic anxiety, anger-related features, bipolar disorder, suicidal behavior, and several addictions.

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“…One of the better studied polymorphic sites in the TPH1 gene is single nucleotide polymorphism 218A > C (rs1800532) in the 7th intron causing reduced gene expression level due to its localization in the GATA transcription factor linkage site. A series of studies show the link between highly active *А allele and/or *A/*A genotype with self-aggression (Beden et al, 2016), and *C/*C genotype with high general and verbal aggression levels in people with depressive disorders (Koh et al, 2012). Polymorphism -703G > T (rs4570625) is a widely studied polymorphism in the TPH2 gene, which determines reduction in the gene's transcription activity.…”

Section: Molecular-genetic Markers Of Predisposition Towards Aggressimentioning

confidence: 99%

Recent advances in genetics of aggressive behavior

Davydova¹,

Litvinov²,

Enikeeva³

et al. 2018

Vestn. VOGiS

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One of the most important problems of modern neurobiology and medicine is an understanding of the mechanisms of normal and pathological behavior of a person. Aggressive behavior is an integral part of the human psyche. However, environmental risk factors, mental illness and somatic diseases can lead to increased aggression to be the biological basis of antisocial behavior in a human society. An important role in development of aggressive behavior belongs to the hereditary factors that may be linked to abnormal functioning of neurotransmitter systems in the brain yet the underlying genetic mechanisms remain unclear, which is due to a large number of single nucleotide polymorphisms, insertions and deletions in the structure of genes that encode the components of the neurotransmitter systems. The most studied candidate genes for aggressive behavior are serotonergic (TPH1, TPH2, HTR2A, SLC6A4) and dopaminergic (DRD4, SLC6A3) system genes, as well as the serotonin or catecholamine metabolizing enzyme genes (COMT, MAOA). In addition, there is evidence that the hypothalamic-pituitary system genes (OXT, OXTR, AVPR1A, AVPR1B), the sex hormone receptors genes (ER1, AR), neurotrophin (BDNF) and neuronal apoptosis genes (CASP3, BAX) may also be involved in development of aggressive behavior. The results of Genome-Wide Association Studies (GWAS) have demonstrated that FYN, LRRTM4, NTM, CDH13, DYRK1A and other genes are involved in regulation of aggressive behavior. These and other evidence suggest that genetic predisposition to aggressive behavior may be a very complex process.

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TPH1 A218 allele is associated with suicidal behavior in Turkish population

Cited by 16 publications

References 35 publications

Variation of Genes Encoding Tryptophan Catabolites Pathway Enzymes in Stroke

Variation of Genes Encoding Tryptophan Catabolites Pathway Enzymes in Stroke

TPH1 (tryptophan hydroxylase 1)

Recent advances in genetics of aggressive behavior

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