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

Abstract

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.

Genetic variability of serotonin pathway associated with schizophrenia onset, progression, and treatment

“…It can be found in neuronal tissue and digestive, secretory, and circulatory systems (Gasparini, Smith, & Griffiths, ). It affects mood, cognition, neuronal growth, and different neurotransmitter pathways, as well as other physiological functions, such as appetite and immune system (Abi‐Dargham, ; Baou et al, ; Xu, Ding, Pang, & Wang, ), which is also implicated in SZ (van Kesteren et al, ). Changes in 5‐HT pathway in SZ lead to altered neuronal signalization and pathoanatomy (Eggers, ; Selvaraj et al, ).…”

“…TPH2 gene has a prominent role in 5‐HT pathway, as the TPH2 catalyzed conversion limits the overall rate of 5‐HT synthesis and thus affects 5‐HT levels. TPH2 haplotypes are associated with paranoid SZ (Xu et al, ; Yi et al, ). Genetic variations in TPH2 promoter may affect gene expression due to alternations in binding site for TF POU class 3 homeobox 2, shortly POU3F2.…”

TPH-2 Polymorphisms Interact with Early Life Stress to Influence Response to Treatment with Antidepressant Drugs

“…Several other groups have shown association of rs4570625 with psychiatric disorders, including schizophrenia (Xu et al, 2014) and epileptic psychosis (Bragatti et al, 2014) and, interestingly in this context, an interaction of the SNP with maternal depression in infant response to fearful expression (Forssman et al, 2014). However, we find that this SNP is not significantly related to outcome measures in our study.…”

“…In a recent meta-analyses, it was found that rs4760820 and rs11178998 demonstrated a strong genetic association with bipolar disorder (Gao et al, 2016). The promoter polymorphism rs4570625 (T-703G) of TPH2 has been found associated with paranoid schizophrenia in Han Chinese (Xu et al, 2014). Tsai et al (2009) reported that the proportion of intron 5 SNP rs2171363 heterozygotes had an increased chance of responding to an 8-week antidepressant treatment as compared with rs2171363 homozygotes (CC or TT).…”

Association of tryptophan hydroxylase-2 polymorphisms with oppositional defiant disorder in a Chinese Han population

“…A more recent study showed that a significant correlation between the frequencies of the rs11179027 and rs1843809 of alleles of TPH - 2 and ADHD [16]. In addition, the TPH-2 gene polymorphism have been found to be associated with late-onset depression [24], PTSD [25, 26], suicide in patients with alcohol dependence [27, 28] and suicidal behavior [29], as well as with schizophrenia [30, 31] and panic in bipolar disorders [32] in the Chinese Han population.…”