Association analysis of TPH-1 and TPH-2 genes with suicidal behavior in patients with attempted suicide in Mexican population

López‐Narváez, María Lilia; Tovilla-Zárate, Carlos Alfonso; González-Castro, Thelma Beatriz; Juárez-Rojop, Isela; Pool-García, Sherezada; Genis, Alma; Blé-Castillo, Jorge L.; Fresán, Ana

doi:10.1016/j.comppsych.2015.05.002

Cited by 24 publications

(24 citation statements)

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“…In the present study, we focused on a rate-limiting enzyme in brain serotonergic synthesis, TPH-2 ( 34 ), as a research candidate to examine the susceptibility of an exonic variant, rs4290270, in its coding gene, TPH-2 , to the risk of primary insomnia. A large number of studies have supported the association of the TPH-2 gene with central nervous system disorders, such as depression ( 23 ), suicidal behavior ( 20 ), and attention-deficit/hyperactivity disorders ( 35 ). In this study, however, no hint of a significant association was detected between the alleles and genotypes of rs4290270 and primary insomnia.…”

Section: Discussionmentioning

confidence: 99%

“…Tryptophan hydroxylase (TPH) is a rate-limiting enzyme in the biosynthesis of 5-HT neurotransmission, and it plays a key role in the regulation of the availability, turnover, and function of serotonin. TPH has two isoforms, TPH-1 (expressed in peripheral tissues) and TPH-2 (expressed predominantly in the brain) ( 20 ). Genetic variation in the TPH-2 gene has recently received much attention because of its potential association with the risk of depression and sleep disturbance ( 13 , 21 , 22 ).…”

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confidence: 99%

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Association of Tryptophan Hydroxylase-2 Gene rs4290270 with Primary Insomnia and Depressive Symptoms in a Chinese Han Population

Feng

2018

Balkan Med J

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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.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Association of Tryptophan Hydroxylase-2 Gene rs4290270 with Primary Insomnia and Depressive Symptoms in a Chinese Han Population

Feng

2018

Balkan Med J

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“…Tryptophan hydroxylase (TPH) belongs to the enzyme superfamily of aromatic amino acid hydroxylases and is the regulator of serotonin synthesis and serotonin activity in the brain [26, 27]. There are two isoforms of TPH (TPH-1 and TPH-2), which mediate the synthesis of most peripheral serotonin and are predominantly expressed in the gut, thymus, spleen, and pineal gland [28, 29]. Especially, TPH-2 is a neuronal-specific enzyme that is predominantly expressed in the neurons of raphe nuclei in the brain stem, and it is the rate-limiting enzyme in serotonin synthesis as well as a key factor for serotonin transmission in the CNS [30, 31].…”

Section: Introductionmentioning

confidence: 99%

Antidepressant Effect ofTetragonia tetragonoides (Pall.) KuntzeExtract on Serotonin Turnover

Yang

Kim

Hong

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Tetragonia tetragonoides (Pall.) Kuntze (TTK) is a groundcover found along coastal areas of the Korean peninsula. TTK is traditionally used to improve women’s health and treat gastrointestinal diseases. Use of herbal medicines in the treatment of mood disorders has recently been suggested as an alternative therapeutic strategy. In the present study, we determined that consumption of TTK extract ameliorated progression of depressive-like symptoms in ovariectomized (OVX) rats and further examined the mechanisms involved, i.e., synthesis, release, and reuptake(s) of serotonin (also known as 5-HT). We assessed the mRNA expression levels of tryptophan hydroxylases (TPH-1 and TPH-2) and serotonin transporter (SERT) as well as the reuptake activity of serotonin in RBL-2H3 cells. We also determined whether or not TTK extract regulates the serum level of serotonin and improves depressive-like symptoms in 0.5, 1, and 2% TTK-fed OVX female rats in a forced swimming test. Our results show that the mRNA levels of TPH-1 and SERT were significantly reduced, whereas the mRNA level of TPH-2 was dose-dependently elevated by TTK (50 and 100 μg/mL) in RBL-2H3 cells. TTK significantly inhibited LPS- (lipopolysaccharide-) induced serotonin uptake in RBL-2H3 cells in a dose-dependent manner. The serum level(s) of serotonin was elevated by 1% and 2% TTK treatment in OVX female rats. Moreover, immobility time in the forced swimming test was reduced by 1% and 2% TTK treatment but not altered by 0.5% TTK treatment in OVX female rats. Taken together, these results indicate that TTK may significantly inhibit depressive-like symptoms due to upregulation of serotonin level(s) and regulation of serotonin reuptake activity. Thus, TTK may exert beneficial effects on depression during pre- or/and postmenopausal periods via modulation of serotonin synthesis and metabolism.

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“…Venous blood was taken from every individual and placed into EDTA containing tubes. DNA isolation was conducted in peripheral leukocytes following a previously published technique (Genis‐Mendoza et al, ; Lopez‐Narvaez et al, ; Molina‐Guzman et al, ). Direct genotyping was performed using the commercial platform Infinium PsychArray BeadChip (PsychChip, Illumina), following the protocol and conditions established by the provider.…”

Section: Methodsmentioning

confidence: 99%

Gene‐level genome‐wide association analysis of suicide attempt, a preliminary study in a psychiatric Mexican population

González‐Castro

Martínez‐Magaña

Tovilla‐Zárate

et al. 2019

Molec Gen & Gen Med

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BackgroundEvidence suggests that liability for suicide behavior is heritable; additionally, suicide has been partly related to other psychiatric disorders. Nevertheless, most of the information reported so far address Caucasian and Asian individuals. Hence, our aim was to conduct a gene‐level association study in Mexican psychiatric individuals diagnosed with suicide attempt.MethodsWe recruited 192 individuals from two clinical centers in Mexico. All participants were born in Mexico and had Mexican parents and grandparents. Direct genotyping was performed using the commercial platform Infinium PsychArray BeadChip. A p‐value lower than 1e‐05 was considered as gene‐level significant and a p‐value lower than 1e‐04 was considered as gene‐level nominal significant.ResultsOur analyses showed that SCARA5 was associated to suicide intent at a gene‐level with statistical significance (p‐value = 1.12e‐6). Other genes were nominally associated with suicide attempt: GHSR (p‐value = 0.0004), RGS10 (p‐value = 5.13e‐5), and STK33 (p‐value = 3.62e‐5). Regarding gene variant analyses, the SNPs with a statistical association (p > .05) were rs561361616, rs1537577, rs11198999 for RGS10, and rs11041981, rs11041993, rs11041994, rs11041995, rs11041997, rs10840083, rs10769918 for STK33. For these genes, previous studies have associated SCARA5 with depression, GHSR with alcohol dependence and depression, and RGS10 with schizophrenia and depression. To date, STK33 has not been associated with any psychiatric disorder.ConclusionOur outcomes revealed that SCARA5, GHSR, RGS10 and STK33 could be considered as risk biomarkers for suicide attempt behavior in our Mexican psychiatric sample. We recommend to perform larger scale analyses to have conclusive results.

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Association analysis of TPH-1 and TPH-2 genes with suicidal behavior in patients with attempted suicide in Mexican population

Abstract: Our results provide evidence for an association between the rs7305115 polymorphism of the TPH-2 gene and suicidal behavior in a Mexican population. However, more studies are necessary to replicate these results using larger samples.

Cited by 24 publications

References 33 publications

Association of Tryptophan Hydroxylase-2 Gene rs4290270 with Primary Insomnia and Depressive Symptoms in a Chinese Han Population

Association of Tryptophan Hydroxylase-2 Gene rs4290270 with Primary Insomnia and Depressive Symptoms in a Chinese Han Population

Antidepressant Effect ofTetragonia tetragonoides (Pall.) KuntzeExtract on Serotonin Turnover

Gene‐level genome‐wide association analysis of suicide attempt, a preliminary study in a psychiatric Mexican population

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