Association of HTR2A-1438G/A Genetic Polymorphism With Smoking and Chronic Obstructive Pulmonary Disease

Introduction

Cigarette smoking is a major risk factor in the development of chronic obstructive pulmonary disease (COPD). Serotonin levels have been associated with COPD and smoking has been as a significant modulator. Elevated levels of serotonin are responsible for bronchoconstriction and pulmonary vasoconstriction and also nicotine dependence, thus serotonin response could be affected by genetic polymorphisms in transporters and receptors of serotonin.

太子参葛根淫羊蕾复合物抗抑郁作用:与NRSF/NRSE-TPH2信号相关

抑郁症属于心理性疾病且无特效疗法.本文对由太子参多糖、葛根淫羊藿总黄酮组成的太子(TZ)胶囊的抗抑郁作用进行了实验研究.利用整体动物悬尾和强迫游泳方法观察TZ的抗抑郁药效,构建了五羟色胺羟化酶2(TPH2,tryptophan hydroxylase-2)质粒对TZ进行体外实验研究,利用qPCR和Western blo...     

Laterodorsal tegmentum and pedunculopontine tegmental nucleus circuits regulate renal functions: Neuroanatomical evidence in mice models

Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a com-bination of retrograde tracers pseudorabies virus (PRV)-614 and fluorescence immunohistochemistry to characterize the neuroanatomic substrate of PPTg and LDTg innervating the kidney in the mouse. PRV-614-infected neurons were retrogradely labeled in the rostral and middle parts of LDTg, and the middle and caudal parts of PPTg after tracer injection in the kidney. PRV-614/TPH double-labeled neurons were mainly localized in the rostral of LDTg, whereas PRV-614/TH neurons were scattered within the three parts of LDTg. PRV-614/TPH and PRV-614/TH neurons were located predomi-nantly in the caudal of PPTg (cPPTg). These data provided direct neuroanatomical foundation for the identification of serotonergic and catecholaminergic projections from the mid-brain tegmentum to the kidney.     

TPH2 -703G/T SNP may have important effect on susceptibility to suicidal behavior in major depression

Background

Serotonergic system-related genes can be good candidate genes for both major depressive disorder (MDD) and suicidal behavior. In this study, we aimed to investigate the association of serotonin 2A receptor gene -1438A/G SNP (HTR2A -1438A/G), tryptophan hydroxylase 2 gene -703G/T SNP (TPH2 -703G/T) and serotonin 1A receptor C-1019G (HTR1A C-1019G) with suicidal behavior.

Methods

One hundred and eighty one suicidal depressed patients and 143 non-suicidal depressed patients who met DSM-IV criteria for major depressive disorder were recruited from patients who were admitted to Korea University Ansan Hospital. One hundred seventy six normal controls were healthy volunteers who were recruited by local advertisement. Patients and normal controls were genotyped for HTR2A -1438A/G, TPH2 -703G/T and 5-HT1A C-1019G. The suicidal depressed patients were evaluated by the lethality of individual suicide attempts using Weisman and Worden's risk-rescue rating (RRR) and the Lethality Suicide Attempt Rating Scale-updated (LSARS-II). In order to assess the severity of depressive symptoms of patients, Hamilton's Depression Rating Scale (HDRS) was administered. Genotype and allele frequencies were compared between groups by χ² statistics. Association of genotype of the candidate genes with the lethality of suicidal behavior was examined with ANOVA by comparing the mean scores of LSARS and RRR according to the genotype.

Results

There were statistically significant differences in the genotype distributions and allele frequencies of TPH2 -703G/T between the suicidal depressive group and the normal control group. The homozygous allele G (G/G genotype) frequency was significantly higher in suicidal depressed patients than in controls. However, no differences in either genotype distribution or in allele frequencies of HTR2A -1438A/G and HTR1A C-1019G were observed between the suicidal depressed patients, the non-suicidal depressed patients, and the normal controls. There were no differences in the lethality of suicidal behavior in suicidal depressed patients according to the genotypes of three polymorphisms.

Conclusion

Our results suggest that TPH2 -703G/T SNP may have an important effect on susceptibility to suicidal behavior. Furthermore, an increased frequency of G allele of TPH2 SNP may be associated with elevated suicidal behavior itself rather than with the diagnosis of major depression and may increase risk of suicidality, independent of diagnosis.     

TPH2基因单核苷酸多态性与双相情感障碍及其自杀行为的关系

目的 探讨色氨酸羟化酶2(TPH2)基因rs7305115单核苷酸多态性与双相情感障碍及自杀行为的关系.方法 提取205例双相情感障碍患者和225名健康对照者基因组DNA,采用聚合酶链反应(polymerase chain reaction PCR)扩增包括TPH2基因rs7305115位点的312bp基因组DNA片段,PCR产物直接测序.结果 在第7外显子周围未发现其它的单核苷酸多态性.双相情感障碍患者和健康对照者TPH2 rs7305115基因型和等位基因频率无统计学意义的差别(P>0.05),但患者组内有自杀行为的个体携带基因型AA的频率及等位基因A的频率均较低,两组比较差异有统计学意义(P<0.05).结论 TPH2基因rs7305115单核苷酸多态性与双相情感障碍无明显关联,与自杀行为有关联,其可能与双相情感障碍自杀行为易感性相关.

Abstract：

Objective To explore the relation among single nucleotide polymorphism of a novel tryptophan hydroxylase isoform (TPH2) gene rs7305115,bipolar disorder and suicidal behavior. Methods Specimens of peripheral blood were collected from 205 bipolar disorder and 225 controls. A novel tryptophan hydroxylase isoform (TPH2) gene rs7305115 in length 312bp was amplitied by Polvmerase chain reaction (PCR), and the product was analyzed by direct sequencing. Results We did not discover new single nucleotide polymorphism. Compared with Control Group,no significant difference of genotypes and alleles of TPH2 gene rs7305115 single nucleotide polymorphism had been found in patient group(P>0. 05). However,there existed significant differences between suicide behavior and non suicide behavior in bipolar disorder patient in genotypea of TPH2 gene rs7305115A/A. Suicide behavior of bipolar disorder patients in AA genotypes was much lower than non suicide behavior of bipolar disorder patients (P<0. 05). Con-clusion TPH2 gene rs7305115 single nucleotide polymorphism may have no association with the susceptibility of bipolar disorder, but associated with suicide behavior in bipolar disorder. A allele may be one of the risk factors for suicide behavior in bipolar disor-der.