Cortical GABAergic inhibitory neurons are composed of three major classes, each expressing parvalbumin (PV), somatostatin (SOM) and 5-hydroxytryptamine receptor 3A (Htr3a), respectively. Htr3a
Animals ; Interneurons/metabolism* ; Mice ; Neurons/metabolism* ; Parvalbumins/metabolism* ; Receptors, Serotonin, 5-HT3/genetics* ; Serotonin ; Somatostatin/metabolism*

The serotonin transporter (SERT) is the target site for serotonin reuptake inhibitors, which are the most widely used agents for treating various psychiatric diseases including depression. The SERT is a member of a large family of homologous integral membrane proteins. This transporter takes up 5-HT in a process that is coupled to the transmembrane movement of Na+, Cl-, and K+. The SERT may operate in at least two modes, an alternating access carrier or a channel. The function of SERT is acutely regulated by various protein kinases and phosphatases. The SERT gene is located on chromosome 17 and has several polymorphisms including 5-HTTLPR and intron 2 VNTR. Most studies involving the association between 5-HTTLPR and the response to SSRI in depression reported that l/l genotype showed better response and fewer side effects. But, it is too early to draw definite conclusion of the effects of 5-HTTLPR on anti-depressant treatment. Therefore, it is necessary to perform further studies reflecting various ethnicities and genetics of subjects as well as the environmental interactions. This review discusses recent advances in defining the structure, the action mechanism, the location, and the regulation of SERT. Furthermore, it discusses the function of SERT polymorphisms and its implications on the anti-depressant therapies.
Chromosomes, Human, Pair 17 ; Depression ; Drug Therapy* ; Genetics ; Genotype ; Humans ; Introns ; Membrane Proteins ; Phosphoric Monoester Hydrolases ; Protein Kinases ; Serotonin Plasma Membrane Transport Proteins* ; Serotonin Uptake Inhibitors ; Serotonin*

AIMTo determine the feasibility of establishing the heterologous expression model of human- serotonin transporter(hSERT or 5-HTT).

METHODScRNA of SERT was transcribed from cDNA, which was cloned in the pOTV vector. Each oocyte of mature xenopus laevis was injected with transcribed cRNA in vivo and incubated at room temperature for 4-9 days. Recording the current induced by 5-HT with voltage clamp technique tested the function of the expressed 5-HT transporter.

RESULTSThe transporter current could be observed in Ringer's solution containing 5-HT, and the 5-HT induced current were concentration-dependent. Norepinephrine and dopamine could not induce the transporter current while the 5-HT induced current could be specifically inhibited by 5-HTT blocker, desipramine.

CONCLUSIONThe results demonstrate that the heterologous expression product in xenopus laevis oocytes is human 5-HT transporter.

Animals ; Carrier Proteins ; genetics ; DNA, Complementary ; genetics ; Female ; Gene Expression ; Models, Animal ; Oocytes ; metabolism ; RNA, Messenger ; genetics ; Serotonin ; metabolism ; Serotonin Plasma Membrane Transport Proteins ; biosynthesis ; genetics ; Xenopus laevis

OBJECTIVEDisruptive behavior disorder (DBD) is one of the main comorbidity of attention deficit hyperactivity disorder (ADHD). Previous studies showed significantly different serotonin function between ADHD children with and without the comorbidity of DBD. Therefore, it is needed to compare these two groups in terms of serotonin receptor gene polymorphisms, which may provide further evidence for the previous studies. The current study aimed to investigate the relationship between two serotonin receptor 2C (HTR2C) gene polymorphisms, that are C-759T and G-697C polymorphisms, and ADHD with or without concomitant DBD.

METHODBlood samples were taken from 237 trios with probands of ADHD with DBD comorbidity and 251 trios with probands of ADHD without comorbidity of DBD. All the subjects were from the ADHD clinic of Peking University Sixth Hospital. DNA was extracted and PCR was performed to amplify the fragments containing both C-759T and G-697C polymorphisms. AciI was used to detect different alleles of the two polymorphisms. Both allele-based and haplotype-based TDT analyses were used to test the association of the two polymorphisms of HTR2C gene and ADHD with or without comorbidity of DBD.

RESULTSThe haplotypes -759C (chi(2) = 4.25, P = 0.04), -697G(chi(2) = 3.21, P = 0.07), as well as -759C/-697G were over-transmitted (chi(2) = 4.31, P = 0.04) to the probands of ADHD without DBD. No biased transmission of any allele and haplotype were found in families with probands of ADHD with DBD.

CONCLUSIONADHD with or without the comorbidity DBD was different at the level of HTR2C gene polymorphisms of C-759T and G-697C. HTR2C is related to ADHD without DBD, while not related to ADHD with DBD. The results suggested that the two groups may have different genetic background, at least in HTR2C.

Alleles ; Attention Deficit Disorder with Hyperactivity ; complications ; genetics ; Attention Deficit and Disruptive Behavior Disorders ; complications ; genetics ; Child ; Comorbidity ; Gene Frequency ; Genetic Predisposition to Disease ; Genetic Testing ; Genotype ; Haplotypes ; Humans ; Linkage Disequilibrium ; Polymorphism, Genetic ; Receptor, Serotonin, 5-HT2C ; genetics ; Receptors, Serotonin ; Serotonin ; genetics

OBJECTIVETo assess whether HTR1A and HTR1B polymorphisms are associated with the predisposition, gender, PUMC Classification and/or severity of adolescent idiopathic scoliosis (AIS).

METHODSRs6294 (HTR1A) and rs6296 (HTR1B) were genotyped in 103 AIS patients treated from January 2006 to March 2007, and 108 controls with matched gender and age. The data were analyzed by the allelic and genotypic association analysis, and the genotype-phenotype (gender, PUMC Classification, and Cobb angle) association analysis.

RESULTSThe distributions of the alleles of all the 2 SNPs met Hardy-Weinberg equilibrium in the controls (goodness-of-fit chi(2) test, P > 0.05). The allele A of rs6294 was related with the occurrence of AIS (P = 0.041), but differences of the allele frequencies of rs6296 and the genotype frequencies of both SNPs between 2 groups had no statistical significance (P > 0.05). The genotype A/A + A/G of rs6294 was associated with AIS PUMC type III, and there was no other positive results in genotype-phenotype association analysis.

CONCLUSIONThese results suggest that HTR1A may be a predisposition gene of AIS PUMC type III, and PUMC Classification may has its genetic basis.

Adolescent ; Gene Frequency ; Genetic Association Studies ; Genotype ; Humans ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Receptor, Serotonin, 5-HT1A ; genetics ; Receptor, Serotonin, 5-HT1B ; genetics ; Scoliosis ; genetics

Premature ejaculation (PE), as one of the most common male sexual dysfunctions, has a serious negative impact on the sexual satisfaction of the patients and their sexual partners. Lifelong PE is a most common type and a current focus of research as well. The etiology and pathogenesis of this disease are not yet clear and genetic factors are considered to be closely related to lifelong PE. Studies show that the 5-hydroxytryptamine transporter (5-HTT) gene plays an important role in the development and progression of lifelong premature ejaculation and the 5-HTT-linked polymorphic region (5-HTTLPR) has attracted much attention in recent years. This article presents an overview on the correlation between 5-HTTLPR and lifelong PE.
Adult ; Ejaculation ; Humans ; Male ; Polymorphism, Genetic ; Premature Ejaculation ; genetics ; Serotonin Plasma Membrane Transport Proteins ; genetics

OBJECTIVETo investigate the association between anxiety-depression and 5-HTTLPR gene polymorphism in school-aged twins.

METHODSA total of 147 pairs of twins (47 pairs of monozygotic twins, 100 pairs of dizygotic twins) aged 8-12 years from Baotou and Hohhot were selected as respondents. The Achenbach Child Behavior Checklist (CBCL) was used to calculate the scores of anxiety-depression factors in school-aged twins. The DNA was extracted from oral epithelial cells, and polymerase chain reaction was applied for 5-HTTLPR genotyping. The generalized estimating equation (GEE) was used to analyze the effect of 5-HTTLPR polymorphism and family environment on anxiety-depression in school-aged twins.

RESULTSThe children with LS and SS genotypes had significantly higher scores of anxiety-depression factors than those with LL genotype (χ2=3.938, P<0.05). The interaction of 5-HTTLPR genotype with family cohesion and family rearing patterns had a significant impact on the scores of anxiety-depression factors in twins (χ2=6.129 and 7.665, both P<0.05).

CONCLUSIONS5-HTTLPR genotype is significantly correlated with the scores of anxiety-depression factors in school-aged twins. In the family with high cohesion and an autocratic family rearing pattern, S allele may increase the possibility of anxiety-depression in twin children.

Anxiety ; genetics ; Child ; Depression ; genetics ; Female ; Genotype ; Humans ; Male ; Polymorphism, Genetic ; Serotonin Plasma Membrane Transport Proteins ; genetics ; Twins ; genetics

Major depression disorder is an increasing heavy burden in modem society, but its pathological mechanism is still vague. Recent evidence indicated that two pore potassium channel, TREK1, is one of the important drug targets of antidepressants. The structural and functional research progress of TREK1 potassium channel were reviewed with an emphasis on its roles in anti-depression, neuronal protection, and neuronal plasticity. The complicated interactions between TREK1 potassium channel and monoamine transmitters-receptors were also reviewed and future directions to explore the underline mechanism were also discussed.
Animals ; Antidepressive Agents ; pharmacology ; Depressive Disorder, Major ; genetics ; metabolism ; physiopathology ; Drug Delivery Systems ; Gene Knockout Techniques ; Humans ; Neuronal Plasticity ; Polymorphism, Genetic ; Potassium Channels, Tandem Pore Domain ; genetics ; metabolism ; physiology ; Receptors, Serotonin ; metabolism ; Receptors, Serotonin, 5-HT4 ; Serotonin ; pharmacology

OBJECTIVES: Tardive dyskinesia(TD) is a serious side effect associated with long-term antipsychotic treatments. Some candidate genetic polymorphisms were reported to be associated with TD and possible involvement of serotonergic receptors in the pathophysiology of TD has been suggested. In the present study, we investigated the association between 5-HT6 receptor gene polymorphism and TD with schizophrenia. METHODS: To investigate the relationship between 5-HT6 receptor gene polymorphism and TD, 60 patients with TD were compared with 60 patients without TD. The 267C/T allele of 5-HT6 receptor gene was genotyped by means of polymerase chain reaction method. TD was evaluated using the Abnormal Involuntary Movement Scale(AIMS). RESULTS: The patients with the three 267C/T genotype showed no significant differences in age, gender, and duration of illness. No significant difference in genotype frequencies was observed between schizophrenic patients with and without TD. In addition, there was no difference in allele frequencies. Further analysis with an measure of AIMS scores showed that these scores were not significantly influenced by the 5-HT6 receptor gene polymorphism. CONCLUSION: These results suggest that 267C/T polymorphism of 5-HT6 receptor gene is not significantly associated with susceptibility to TD in schizophrenia.
Alleles ; Dyskinesias ; Gene Frequency ; Genetics ; Genotype ; Humans ; Movement Disorders* ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Schizophrenia* ; Serotonin

OBJECTIVE: To assess the association of SLC6A4 gene c.*670T>G polymorphism with the risk for asthma and peripheral blood cytological characteristics among ethnic Zhuang Chinese from Guangxi, China. METHODS: From May 2017 to March 2020, 258 patients diagnosed with asthma and 244 healthy controls were recruited from the Affiliated Hospital of Youjiang Minzhu Medical College and the People's Hospital of Hechi. Genotypes of the c.*670T>G polymorphism were determined by Sanger sequencing. Flow cytometry was used in combination with an electrical impedance method for the counting and classification of peripheral blood cells. RESULTS: Compared with the T allele, the G allele of the c.*670T>G polymorphism was associated with the risk for asthma in the population (OR = 1.54, 95%CI = 1.15-2.06; P = 0.004). Compared with the GT and TT genotypes, homozygous GG genotype also comprised a risk factor (OR = 1.66, 95%CI = 1.16-2.38; P = 0.005). Stratification of the risk factors showed that the homozygous GG genotype has increased the risk of asthma in males and urban residents (P < 0.01). The erythrocyte, hemoglobin and platelet counts of the asthma group were significantly higher than the control group (P < 0.001). The GG, GT and TT genotypes have respectively accounted for 82.35%, 17.65% and 0% of the samples with platelets exceeding the normal value. The overall platelet level of GG genotype was higher than GT+TT genotype (P < 0.05). The significant association was verified by the false positive report probability, and at a prior probability level of 0.1, G vs. T false positive probability was 0.071, and GG vs. GT+TT false positive probability was 0.153. CONCLUSION The GG genotype of the c.*670T>G polymorphism is associated with the risk for asthma among ethnic Zhuang Chinese from northwest Guangxi. Above finding has also enriched the genotypic data and peripheral blood phenotype for this polymorphism.
Male ; Humans ; East Asian People ; China ; Genotype ; Alleles ; Asthma/genetics* ; Serotonin Plasma Membrane Transport Proteins