Linkage of schizophrenia with TPH2 and 5-HTR2A gene polymorphisms in the Malay population

Tee, Shiau Foon; Chow, Tze Jen; Tang, Pek Yee; Loh, Han Chern

doi:10.4238/vol9-3gmr789

Cited by 23 publications

(13 citation statements)

References 22 publications

(25 reference statements)

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“…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: 92%

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: Introductionmentioning

confidence: 92%

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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“…However, to date, studies of the origins, the migration history as well as relationships among the Orang Asli and Bumiputera of Sarawak are limited (Lian, 2001;Macaulay et al, 2005;Hill et al, 2006;Ang, 2009;Lim et al, 2010) while most existing records are from an anthropological and historical point of view (Wright et al, 1971;Kasimin, 1991;Nicholas, 1996). At the end of the last century, specifically the previous three decades, molecular studies became widely used to study human migration and population relationships (Lutz et al, 1998;Al-Zahery et al, 2003;Endicott, 2003;Kashyap et al, 2003;HUGO Pan-Asian SNP Consortium et al, 2009;Tee et al, 2010). Mitochondrial DNA (mtDNA) analysis is particularly well suited for systematic studies of potentially closely related individuals due to the high molecular rate of evolution and maternal mode of inheritance (Md-Zain et al, 2010a,b;Rosli et al, 2011;Vun et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Phylogenetic relationships of the Orang Asli and Iban of Malaysia based on maternal markers

Ang¹,

Leow²,

Yeap³

et al. 2011

Genet. Mol. Res.

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“…But the authors themselves remarked that the power of this analysis was very small with 0.18. In Japanese patients as well as in Malay patients no association was found between two variants and one variant of the TPH2 gene respectively, and schizophrenia (Higashi et al, 2007;Tee et al, 2010). In another association study among Japanese patients neither one of the 15 analyzed TPH2 variants nor their haplotypes were significantly associated with schizophrenia (Shiroiwa et al, 2011).…”

Section: Introductionmentioning

confidence: 88%

Investigation of tryptophan hydroxylase 2 (TPH2) in schizophrenia and in the response to antipsychotics

Schuhmacher

Becker

Rujescu³

et al. 2012

Journal of Psychiatric Research

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Serotonergic transmission is considered relevant in the pathophysiology and the treatment of schizophrenia. Tryptophan hydroxylase (TPH) is the rate limiting enzyme in the biosynthesis of serotonin. While the TPH1 gene has been found to be associated with schizophrenia, studies focusing on TPH2 variants did not yield conclusive results for schizophrenia or the response to antipsychotic medication. We analyzed eleven TPH2 SNPs in two case-control samples consisting of 4453 individuals in total. Six SNPs were selected because of their potential functional relevance (rs4570625, rs11178997, rs11178998, rs7954758, rs7305115, and, rs4290270) and were supported by another 5 tagging SNPs selected based on HapMap LD information. In the discovery sample (1476 individuals), we observed a significant association with schizophrenia for rs10784941 (p = 0.009, OR minor G-allele 0.82 [0.71-0.95]) and rs4565946 (p = 0.011, OR minor T-allele 0.83 [0.71-0.96]). Association was also observed with a common rs4570625-rs4565946 haplotype (OR G-C haplotype 1.20 [1.02-1.40]; p = 0.0046). Single-marker associations could not be replicated in the replication sample consisting of 2977 individuals, but there was a strong trend regarding the rs4570625-rs4565946 G-C haplotype (OR 1.10 [0.98-1.24]; p(one-sided test) = 0.054). In smaller sub-samples, the rare rs4570625-rs4565946 T-T haplotype was associated with reduced processing speed (n = 193, p = 0.004) and sensorimotor gating (n = 68, p = 0.006) of schizophrenia patients. TPH2 variants and the rs4570625-rs4565946 G-C haplotype did not influence the beneficial response to antipsychotic drugs (n = 210) after four weeks of treatment administering the Positive and Negative Syndrome Scale of Schizophrenia (PANSS). We also investigated the association of the SNPs to treatment response, but did not get significant results. In sum, our results argue for only a minor role of TPH2 in schizophrenia.

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Linkage of schizophrenia with TPH2 and 5-HTR2A gene polymorphisms in the Malay population

Cited by 23 publications

References 22 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

Phylogenetic relationships of the Orang Asli and Iban of Malaysia based on maternal markers

Investigation of tryptophan hydroxylase 2 (TPH2) in schizophrenia and in the response to antipsychotics

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