TPH2 Gene Polymorphisms Research Articles

Association of single nucleotide polymorphism in TPH2 Gene with age of MDD cases and controls.

Objective: To determine association of TPH2 (rs7305115) gene polymorphism with age of MDD cases and controls in Pakistani population. Study Design: Case-control study. Setting: Multidisciplinary Lab in Islamic International Medical College Trust in Collaboration with Psychiatry Department, Railway General Hospital, and Rawalpindi. Period: September 2019 to September 2020. Material & Methods: After taking written informed consent blood samples were drawn from all the participants followed by extraction of DNA using ChelexTM method. Allelic frequencies of TPH2 (rs7305115) gene polymorphism in both cases and controls were determined using Multiplex PCR. Results: Number of participants included in the study were 240, out of which 120 were diagnosed cases of MDD whereas 120 were age and gender matched controls. Both the cases and controls were divided in to three groups on the basis of their ages. In group 1 both subjects aged 15 to 35 years were included and a total of 128 subjects fall under this age group out of which 64 (53.33%) were cases and 64 (53.33%) were controls. In group 2 subjects aged 36 to 55 years were included and a total of 86 individuals were found to be present in this age group out of which 45 (37.5%) were cases and 41(34.1%) were controls and in group 3 subjects aged 56 to 75 years were included and a total of 26 individuals were present in this group out of which 11(9.16%) were cases and 15(12.5%) were controls. Significant association was found between age group 1(15-35 years) and GG genotype with risk of development of MDD (OR: 0.3778, 95% CI: 0.1512-0.9349, P= 0.0338). Conclusion: We have found in the present study that age group 1(15-35 years) with GG genotype of TPH2 gene polymorphism have a significantly increased risk of developing MDD as compared to other age groups in our study.

Association of TPH1 and TPH2 Gene Polymorphisms with the Risk of Developing Psychoneurological Disorders

Association of TPH1 and TPH2 Gene Polymorphisms with the Risk of Developing Psychoneurological Disorders

The relationship between occupational stress, musculoskeletal disorders and the mental health of coal miners: The interaction between BDNF gene, TPH2 gene polymorphism and the environment

ObjectiveMental disorders are prevalent among the population and seriously endanger people's working ability as well as their physical and mental health. This study employed stratified cluster random sampling to examine occupational stress, musculoskeletal disorders (MSDs) and the mental health status of 1675 coal miners in Xinjiang. MethodsA cross-sectional investigation was carried out, and BDNF (rs6265, rs10835210) gene polymorphism and TPH2(rs4570625, rs4131347) gene polymorphism were identified in 30% of the study's participants. This study aimed to analyze the relationship between mental disorders, occupational stress and MSDs, and to explore the role of gene-gene and gene-environment interactions in respect to the incidence of psychological disorders. On this basis, the risk prediction model of mental disorders was constructed. ResultsThe study identified the following risk factors for mental disorders among coal miners: Female, age, four shifts, coal miners, college education or above, single, occupational stress, and MSDs. MSDs, BDNF gene (rs6265) and TPH2 gene (rs4570625) are directly related to mental disorders, and interactions were found between MSDs and BDNF gene (rs6265),TPH2 gene (rs4570625), affecting the incidence of mental disorders. The Bayesian network model of mental disorders showed that MSDs, educational level, TPH2 gene (rs4570625) and marital status had a higher influence on mental disorders. Monthly income and educational level can indirectly affect mental disorders through occupational stress. BDNF gene (rs6265) and TPH2 gene (rs4570625) can indirectly affect mental disorders through MSDs. There may be an interaction between MSDs and educational level. ConclusionsBesides demographic characteristics, occupational stress and musculoskeletal disorders are also factors affecting the mental health of coal miners. It was found that BDNF rs10835210, TPH2 rs4570625 and TPH2 rs4131347 interact with each other, increasing the risk of mental disorders among coal miners.

Association study of TPH1 (rs1800532) and TPH2 (rs4570625) Polymorphisms in Type 1 Bipolar Disorder in Iran

Background: Bipolar disorder (BD) has episodes of depression and mania or hypomania. Several studies have been conducted on the role of genes in bipolar disorders and suicidal behaviors, and serotonin-associated genes, Tryptophan hydroxylase (TPH1 and TPH2), are proposed as one of the main effective genetic factors. Methods: In this study, 116 BD patients and 118 age and gender-matched healthy subjects were recruited as the control group. The polymorphisms of THP1 (rs1800532) and TPH2 (rs4570625) genes were identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: There was a positive association of bipolar disorder with CC genotype (P = 0.04) for TPH1 A218C polymorphism, yet not for other genotypes and alleles. There was no association for the genotype and allelic frequency distributions of TPH2-703G/T between bipolar patients and healthy control groups. Conclusions: The TPH1 and TPH2 gene polymorphisms are subjects of many researches. There are contradictions in investigations around the world. These results are in agreement with studies of other populations, yet are different from many studies. There is a need for further investigations.

Association of TPH2 gene polymorphism with response to antidepressant treatment among ethnic Han Chinese population

To assess the association of TPH2 gene polymorphisms with the response or remission to selective serotonin reuptake inhibitors (SSRIs) drugs during treatment of major depressive disorder. For 304 patients receiving SSRIs treatment for major depression disorder, 3 single nucleotide polymorphisms (SNPs) (rs1007023, rs1023990 and rs4570625) in the TPH2 gene were genotyped by MALDI-TOF mass spectrometry using a MassArray Analyzer 4 system. HAMD-17 was adopted as the primary rating tool to evaluate the severity of depression on the baseline and at the end of 1st, 2nd, 4th and 6th week of treatment. The frequency of GG genotype/G allele for rs4570625 differed significantly with the frequency of TT and GT genotypes/T allele between responders and non-responders (P=0.013 and 0.007, respectively). Genotypic and allelic frequencies of the other polymorphisms did not differ significantly between the two groups (P>0.05). No association of TPH2 gene polymorphism with remission was found with the 3 SNPs. The polymorphisms of TPH2 gene may play an important role in response to antidepressant drug therapy.

The Relationship Between Tryptophan Hydroxylase-2 Gene with Primary Insomnia and Depressive Symptoms in the Han Chinese Population

Background:Insomnia often coexists with depression, and there is compelling evidence for a genetic component in the etiologies of both disorders.Aims:To investigate the relationship between exonic variant (rs4290270) in the tryptophan hydroxylase-2 gene and primary insomnia and symptoms of depression in Han Chinese.Study Design:Case-control study.Methods:This study included 152 patients with primary insomnia and 164 age- and gender-matched normal controls. All patients were investigated by polysomnography for 2 consecutive nights. The depressive symptoms were measured by using a 20-item Zung Self-rating Depression Scale. Sleep quality was assessed with the Pittsburgh Sleep Quality index. The genotypes of the TPH-2 gene polymorphism rs4290270 were determined by the polymerase chain reaction-restriction fragment length polymorphism method.Results:The genotype distributions of the tryptophan hydroxylase-2 gene polymorphism rs4290270 were in Hardy-Weinberg equilibrium in both patients and controls (p>0.05). The allele and genotype distributions of this variant were comparable between patients and controls in all subjects and between genders (all p>0.05). The impact of rs4290270 on self-rating depression scale score changes was statistically significant (p=0.002), with carriers of the A/A genotype having the highest self-rating depression scale score (mean ± standard deviation: 52.73±12.88), followed by the A/T genotype (50.94±11.29, p=0.35) and the T/T genotype (43.48±7.78, p<0.01), and this impact was more obvious in women (p<0.001).Conclusion:The tryptophan hydroxylase-2 gene polymorphism rs4290270 may not be a susceptibility locus for primary insomnia in Han Chinese, but it may be a marker of depressive symptoms.

Association of TPH-1 and TPH-2 gene polymorphisms with suicidal behavior: a systematic review and meta-analysis.

BackgroundIt is widely acknowledged that suicidal behavior (SB) has a genetic influence. As a consequence, molecular genetic studies have been mostly conducted on serotonergic genes. One of the most promising candidate genes of this system is tryptophan hydroxylase (TPH). Although there have been several positive studies associating TPH genes and SB, the evidence is not entirely consistent. Therefore, we performed a meta-analysis to gain a better understanding into this issue.MethodsThe meta-analysis was conducted with 37 articles of genetic association studies of TPH-1 (A218C and A779C) and TPH2 (G-703 T, A-473 T and G19918A) genes. To analyze the association of these variants with SB we used the following models: allelic, additive, dominant and recessive. In addition, we performed a sub-group analysis by Caucasian and Asian populations using the same four models.ResultsTPH-1 gene variants showed a positive significant association with SB, but only in the fixed effects models. With regard to TPH-2 gene variants we could not find an association with SB.ConclusionsThe study provides evidence that A218C/A779C TPH-1 variants may be a risk factor to manifest SB at the clinical level, which is in agreement with previously reported meta-analyses. With regard to G-703 T/A-473 T/G19918A TPH-2 variants, our up-to-date meta-analysis could not detect any significant association between those genetic variants and SB. However, these results should be interpreted with caution since further studies need to be undertaken using larger sample sizes in different ethnic populations to confirm our findings.

Association Between TPH2 Gene Polymorphisms and Attention Deficit Hyperactivity Disorder in Korean Children

Attention deficit hyperactivity disorder (ADHD) is a common disorder of the school-age population. ADHD is a familial disorder and genetic studies estimate heritability at 80%-90%. The aim of the present study was to investigate the association between the genetic type and alleles for the TPH2 gene in Korean children with ADHD. The sample consisted of 142 ADHD children and 139 control children. We diagnosed ADHD according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). ADHD symptoms were evaluated with Conners' Parent Rating Scales and Dupaul Parent ADHD Rating Scales. Blood samples were taken from the 281 subjects, DNA was extracted from blood lymphocytes, and polymerase chain reaction was performed for TPH2 polymorphism. Alleles and genotype frequencies were compared using the chi-square test. We compared the allele and genotype frequencies of TPH2 gene polymorphism in the ADHD and control groups. This study showed that there was a significant correlation among the frequencies of the rs11179027 (odd ratio [OR]=2.12, 95% confidence interval [CI]=1.13-3.97, p=0.020) and rs1843809 (OR=0.48, 95% CI=0.24-0.97, p=0.040) of alleles of TPH2, but the final conclusions are not definite. Follow-up studies with larger patient or pure subgroups are expected. These results suggested that TPH2 might be related to ADHD symptoms.

TPH2 polymorphisms and expression in Prader-Willi syndrome subjects with differing genetic subtypes

Prader-Willi syndrome (PWS) is a genetic imprinting disease that causes developmental and behavioral disturbances resulting from loss of expression of genes from the paternal chromosome 15q11-q13 region. In about 70% of subjects, this portion of the paternal chromosome is deleted, while 25% have two copies of the maternal chromosome 15, or uniparental maternal disomy (UPD; the remaining subjects have imprinting center defects. There are several documented physical and behavioral differences between the two major PWS genetic subtypes (deletion and UPD) indicating the genetic subtype plays a role in clinical presentation. Serotonin is known to be disturbed in PWS and affects both eating behavior and compulsion, which are reported to be abnormal in PWS. We investigated the tryptophan hydroxylase gene (TPH2), the rate-limiting enzyme in the production of brain serotonin, by analyzing three different TPH2 gene polymorphisms, transcript expression, and correlation with PWS genetic subtype. DNA and RNA from lymphoblastoid cell lines derived from 12 PWS and 12 comparison subjects were used for the determination of genetic subtype, TPH2 polymorphisms and quantitative RT-PCR analysis. A similar frequency of TPH2 polymorphisms was seen in the PWS and comparison subjects with PWS deletion subjects showing increased expression with one or more TPH2 polymorphism. Both PWS deletion and PWS UPD subjects had significantly lower TPH2 expression than control subjects and PWS deletion subjects had significantly lower TPH2 expression compared with PWS UPD subjects. PWS subjects with 15q11-q13 deletions had lower TPH2 expression compared with PWS UPD or control subjects, requiring replication and further studies to identify the cause including identification of disturbed gene interactions resulting from the deletion process.

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

The serotoninergic system has been implicated in the etiology of schizophrenia and other behavioral disorders. Association studies have focused on the tryptophan hydroxylase 2 gene (TPH2) and the 5-hydroxytryptamine receptor 2A gene (5-HTR2A). We genotyped two single-nucleotide polymorphisms, A1438G of 5-HTR2A and intronic rs1386494 of TPH2 in the Malay population, using a sample size of 289 schizophrenic patients and 130 healthy controls. We found a significant association of A1438G of 5-HTR2A with schizophrenia in Malays. On the other hand, TPH2 polymorphism was not associated with schizophrenia. This is the first genetic association study concerning schizophrenia in the Malay population.

Effects of the HTR3A and TPH2 gene polymorphism on paroxetine and fluvoxamine efficacy in major depression

Kato, Masakia; Wakeno, Masatakaa; Okugawa, Gakua; Takekita, Yoshiterua; Nobuhara, Kenjia; Fukuda, Tsuyoshib; Yamashita, Megumib; Azuma, Junichib; Kinoshita, Toshihikoa Author Information

Single nucleotide polymorphism and haplotype analysis of a novel tryptophan hydroxylase Isoform (TPH2) gene in suicide victims

Tryptophan hydroxylase, the rate-limiting enzyme in the biosynthesis of serotonin, represents a major candidate in numerous genetic association analyses of suicidal behavior; however, the results are so far inconclusive. Recently, a second tryptophan hydroxylase isoform (TPH2) was identified in mice, which was exclusively present in the brain. In a previous postmortem study of our own group, we could demonstrate that TPH2 is also expressed in the human brain but not in peripheral tissues. We performed single nucleotide polymorphisms, haplotypes, and linkage disequilibrium studies on 263 suicide victims and 266 healthy control subjects with 10 single nucleotide polymorphisms in the TPH2 gene. Significant association was detected between one single nucleotide polymorphism (p = .004, global p = .01) and suicide. Additionally, haplotype analysis also produced support for association (p < .0001, global p = .0001). This is the first report about an association between TPH2 gene polymorphisms and completed suicide. Our findings provide evidence for an involvement of genetic variants in the TPH2 gene in suicidal behavior. These results might open up new research strategies for the analysis of the observed disturbances in the serotonergic system in several other psychiatric disorders.