Academic journal article Hong Kong Journal of Psychiatry

No Association between Tryptophan Hydroxylase-2 Gene G1463A Polymorphism and Unipolar Depression in a Southern Chinese Han Population (Translated Version)

Academic journal article Hong Kong Journal of Psychiatry

No Association between Tryptophan Hydroxylase-2 Gene G1463A Polymorphism and Unipolar Depression in a Southern Chinese Han Population (Translated Version)

Article excerpt

Introduction

Depression is a common psychiatric disease which may lead to mental disability and suicide. The life-time prevalence of depression is about 5 to 17%. (1) The incidence of depression is highly modulated with environmental factors, however, there is also a strong genetic contribution to the disease pathogenesis with an estimated heritability of 40 to 70%. (1) Family studies, twin studies, and foster children studies show an association between genetic factors and depression. (2) Until now, there are still no confirmed genes or related DNA sequences associated with the onset of depression. Therefore, studies to identify the genetic associations of depression will be an interesting area of concern.

Results from psychopharmacology and neurobehavioural research show serotonin (5-hydroxytryptamine [5-HT]) dysfunction in the central nervous system is associated with the incidence of depression. (2) Decreased level of 5-HT is associated with depressed mood, reduced appetite, insomnia, circadian rhythm disturbance, endocrine and sexual dysfunction, anxiety, and reduced activity. (3) Furthermore, the central serotonin neural system is the target for most commonly prescribed antidepressants such as tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and monoamine oxidase inhibitors. (4) Central serotonin is synthesised at dorsal raphe nuclei of the brainstem. (5) The biological processes related to serotonin in the body include its biosynthesis, storage, transportation, release, receptor binding, reuptake, and metabolism. Proteins and corresponding related genes which regulate these processes include tryptophan hydroxylase-1 and -2 (TPH1 and TPH2), vesicular monoamine transporter 2 (VMAT2), serotonin transporter (5-HTT), monoamine oxidase A (MAOA), and the serotonin receptors including: 5-HT1A, -2A, -2C, -3, -4, -5, -6, -7. (6) Therefore, these serotonin-related genes are the candidates for research into the aetiology of depression.

Tryptophan hydroxylase is the rate-limiting enzyme of 5-HT biosynthesis, which includes TPH1 and TPH2. The former (TPH1) is predominately expressed in peripheral organs such as the heart, lungs, duodenum, liver, and adrenal glands, and also in some parts of the brain. It is also the main regulator of peripheral 5-HT synthesis. The latter (TPH2) is neuron-specific and only expressed in the brain 5-HT neuron. In some regions of the brain (such as the hippocampus, frontal lobe, thalamus, hypothalamus, and amygdala), the expression levels of TPH1 and TPH2 are almost equal. However, TPH2 is predominately expressed in the brain stem where 5-HT neurons originate. (7) Recent studies have shown inconsistent results regarding any association between TPH2 gene polymorphism and unipolar depression. (8-16) In 2005, Zhang et al4 found that the human TPH2 gene coding region contains a functional polymorphism, G1463A, leading to the replacement of the 441 arginine position with histidine (R441H). This may cause approximately 80% of TPH2 function loss and significantly reduce 5-HT generation. Zhang et al (4) also analysed the TPH2 G1463A polymorphism and its relationship with the affective disorder. Results showed that among 87 patients with unipolar depression, 9 carried the 1463A mutant allele, while in 219 control subjects, only 3 carried the mutant allele. This suggested that the R441H mutation may be an important risk factor in unipolar depression. In order to verify this result in the Chinese Han population, this study used an association analysis method to study the TPH2 G1463A polymorphism in the southern Chinese Han population and its relevance to unipolar depression.

Methods

Subjects

All study subjects were of Han nationality in the Guangdong Province of southern China and gave signed informed consent prior to enrolment.

Case Group

A total of 123 patients were included in the study--42 were male, 81 were female. …

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