Common genetic variations in TPH1/TPH2 genes are not associated with schizophrenia in Japanese population

Shiroiwa, Kyoichi; Hishimoto, Akitoyo; Mouri, Kentaro; Fukutake, Masaaki; Supriyanto, Irwan; Nishiguchi, Naoki; Sato, Osamu

doi:10.1016/j.neulet.2010.02.003

Cited by 18 publications

(11 citation statements)

References 32 publications

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“…Furthermore, frequencies of haplotypes constructed with rs41317118-rs17110747-rs41317114 were not associated with schizophrenia, consistent with other findings (De Luca et al, 2005a;Shiroiwa et al, 2010;Serretti et al, 2011).…”

Section: Discussionsupporting

confidence: 90%

“…Prior to our study, no studies had reported an association between genetic variations in the TPH2 gene and schizophrenia (De Luca et al, 2005a;Higashi et al, 2007;Shiroiwa et al, 2010;Tee et al, 2010, Kim andYoon, 2011;Zhang et al, 2011). There are several possible explanations for our novel results.…”

Section: Discussionmentioning

confidence: 58%

“…In contrast to TPH1, genetic studies have shown an association between TPH2 and suicidal behavior (Zill et al, 2004b;Li and He, 2006a), major depression (Zill et al, 2004c), panic disorder (Maron et al, 2007), chronic fatigue syndrome (Goertzelet et al, 2006;Smith et al, 2006) and Tourette syndrome (Mössner et al, 2007). However, no evidence has been found for a role of TPH2 in schizophrenia, despite several studies in this area (De Luca et al, 2005a;Higashi et al, 2007;Shiroiwa et al, 2010;Tee et al, 2010;Kim and Yoon, 2011;Zhang et al, 2011). It is noteworthy that a certain number of these studies focused mainly on the rs4570625 (-703G/T), a common polymorphic SNP in the putative promoter (Kennedy et al, 2003) that has been reported to be associated with the attention deficit hyperactivity disorder (ADHD) (Walitza et al, 2005), emotional processing (Herrmann et al, 2007), personality traits, and disorders related to emotional dysregulation (Gutknecht et al, 2007;Reuter et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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TPH2 gene polymorphisms in the regulatory region are associated with paranoid schizophrenia in Northern Han Chinese

Xu¹,

Ding²,

Pang³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. In the last years, serotonin (5-HT) has been related with the pathophysiology of several psychiatric disorders, including schizophrenia. Thus, genes related to the serotonergic (5-HTergic) system are good candidate genes for schizophrenia. The rate-limiting enzyme of 5-HT synthesis is tryptophan hydroxylase 2 (TPH2). Single nucleotide polymorphisms (SNPs) in the regulatory regions of TPH2 gene may affect gene expression and biosynthesis of 5-HT triggering to various neuropsychiatric disorders related to 5-HT dysfunction. The present study explored the association of SNPs within the TPH2 gene with paranoid schizophrenia in Han Chinese. A total of 164 patients with schizophrenia and 244 healthy controls were genotyped for six TPH2 SNPs (rs4570625, rs11178997, rs11178998, rs41317118, rs17110747, and rs41317114). Significant group differences were observed in the allele and genotype frequencies of rs4570625 and in the frequencies of GTA and TTA haplotypes corresponding to rs4570625-rs11178997-rs11178998. Our findings suggest that common genetic variations of TPH2 are likely to contribute to genetic susceptibility to paranoid schizophrenia in Han Chinese. Further studies in larger samples are needed to replicate this association.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

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TPH2 gene polymorphisms in the regulatory region are associated with paranoid schizophrenia in Northern Han Chinese

Xu¹,

Ding²,

Pang³

et al. 2014

Genet. Mol. Res.

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“…TPH2 is located in 12q21.1, one of the chromosome regions identified as possibly linked to schizophrenia (Bailer et al 2000). A recent study reported that neither TPH1 nor TPH2 are associated with schizophrenia in a Japanese sample population (Shiroiwa et al 2010). In contrast, a previous study reported that a positive association between TPH1 and schizophrenia was found in Han Chinese subjects (Hong et al 2001).…”

Section: Introductionmentioning

confidence: 95%

Association Study of Tryptophan Hydroxylase-2 Gene in Schizophrenia and Its Clinical Features in Chinese Han Population

Zhang

Shao

et al. 2010

J Mol Neurosci

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Schizophrenia is a chronic and severe mental illness which is characterized by the development of various detrimental clinical features, and its etiology still remains unknown. Based on the evidence from neurobiological and pharmacological research, dysfunctions in central serotonergic transmission may be involved in the development of schizophrenia. Tryptophan hydroxylase 2 (TPH2), a newly identified isoform of tryptophan hydroxylase (the rate limiting enzyme in the biosynthesis of serotonin), regulates the brain-specific serotonin synthesis. To further clarify the role of TPH2 in this disease, we performed a case-control study to examine the association of the TPH2 gene with schizophrenia and its clinical features. We genotyped three putative functional polymorphisms (rs4570625, rs7305115, and rs4290270) within the gene and carried out a case-control study consisting of 304 schizophrenia patients and 362 healthy subjects. The severity of psychotic symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). The frequencies of genotypes and alleles of rs4570625, rs7305115, and rs4290270 did not differ significantly between schizophrenic patients and controls. However, the PANSS positive symptom subcore was significantly associated with rs4570625 (P=0.022). These results suggest that rs4570625 of TPH2 may play an important role in the development of positive symptoms in Han Chinese schizophrenic patients.

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“…For TPH2 , we consulted the HapMap database (version 3/release February 2, 2009) and captured 13 tagging SNPs with the criteria of the r 2 threshold >0.8 in pair-wise tagging only mode using the Tagger program, an implement of the Haploview software for association analysis. Two selected tagging SNPs (rs4641528 and rs10879355) among the 13 tagging SNPs were genotyped as previously described [13] .…”

Section: Genotypingmentioning

confidence: 99%

Post-Stroke Fatigue May Be Associated with the Promoter Region of a <b><i>Monoamine Oxidase A </i></b>Gene Polymorphism

Choi-Kwon¹,

Ko²,

Jun

et al. 2016

Cerebrovasc Dis

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Background: Post-stroke fatigue (PSF) is a common sequela of stroke. Despite reports of serotonergic involvement in the etiology of PSF, the potential contribution of serotonergic genes in the development of PSF needs to be investigated. Methods: A total of 373 patients, who experienced ischemic stroke for PSF, were evaluated 3 months after the stroke. PSF was assessed using the Fatigue Severity Scale. The genomic DNA collected and stored in a -70°C freezer was genotyped for 6 polymorphisms in genes associated with serotonin synthesis (tryptophan hydroxylase 1 (TPH1) A218C, TPH2 rs10879355, and TPH2 rs4641528), transport (the promoter region of the serotonin transporter protein), and catabolism (the 30-bp functional variable number tandem repeat) polymorphism in the promoter region of monoamine oxidase A (MAO-A). Results: Among the 373 patients, 164 (44%) had PSF. All patients were ethnic Koreans. Of the 6 polymorphisms examined, only one marker, that is, low-activity MAO-A was associated with PSF (p < 0.05) in female patients. Multiple logistic regression analyses showed that post-stroke depression (PSD; 95% CI 1.561-14.323, p = 0.006) and low MAO-A activity (95% CI 0.166-0.722, p = 0.005) were factors associated with PSF in female patients, whereas only PSD (95% CI 5.511-65.269, p = 0.000) was associated with PSF in male patients. Conclusions: Our findings suggest that PSF may be associated with a genetic polymorphism involving MAO-A, at least in female stroke patients.

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Common genetic variations in TPH1/TPH2 genes are not associated with schizophrenia in Japanese population

Cited by 18 publications

References 32 publications

TPH2 gene polymorphisms in the regulatory region are associated with paranoid schizophrenia in Northern Han Chinese

TPH2 gene polymorphisms in the regulatory region are associated with paranoid schizophrenia in Northern Han Chinese

Association Study of Tryptophan Hydroxylase-2 Gene in Schizophrenia and Its Clinical Features in Chinese Han Population

Post-Stroke Fatigue May Be Associated with the Promoter Region of a <b><i>Monoamine Oxidase A </i></b>Gene Polymorphism

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