Mechanism of Suoquanwan on Enuresis Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

Objective:To explore the targets and relevant signaling pathways of Suoquanwan in the treatment of enuresis using network pharmacology，and animal expriments are applied to further define its mechanism of action. Method:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） database was used to screen out active chemical components of Suoquanwan，varieties of systematic biological databases were integrated to construct the "active component-disease-target" network relationship，and the common protein protein interaction network（PPI） network genes were functionally enriched. Quantitative real time polymerase chain reaction（Real-time PCR） and Western blot were used to verify the effect of Suoquanwan on AVPR2 and DRD2 gene. Result:A total of 32 active ingredients were screened from Suoquanwan. These active ingredients were interacted with 131 potential targets relating to Enuresis，which contained 14 core target genes，namely arginine vasopressin receptor 2 （AVPR2）， neurotrophic receptor tyrosine kinase 1（NTRK1）， dopamine receptor D2（DRD2）， opioid receptor mu 1（OPRM1）， 5-hydroxytryptamine receptor 1A（HTR1A）， 5-hydroxytryptamine receptor 1B（HTR1B），solute carrier family 6 member 4（SLC6A4），Adrenoceptor Alpha 2A（ADRA2A）， prostaglandin-endoperoxide synthase 2（PTGS2）， cholinergic receptor muscarinic 2（CHRM2）， solute carrier family 6 member 3 （SLC6A3）， 5-hydroxytryptamine receptor 6（HTR6）， solute carrier family 6 member 2（SLC6A2）， cytochrome P450 family 2 subfamily C member 19（CYP2C19）. Gene enrichments mainly involved to G protein-coupled receptor signaling pathway，regulation of trans-synaptic signaling，regulation of neurotransmitter transport and neuroactive ligand-receptor interaction. Real-time PCR and Western blot results showed that Suoquanwan could enhance the expression of AVPR2 in rat kidney，and weaken the expression of DRD2 in rat adrenal. Conclusion:The main chemical constituents in Suoquanwan may alleviate enuresis by regulating AVPR2 and DRD2 and then participating in the G protein-coupled receptor signaling pathway，regulation of trans-synaptic signaling，regulation of neurotransmitter transport and other biological processes.

Dopamine receptor D2 polymorphism is associated with alleviation of obesity after 8-year follow-up: a retrospective cohort study in obese Chinese children and adolescents / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#The aim of this study was to explore the association of dopamine receptor D2 (DRD2) polymorphism and alleviation of obesity in children and adolescents after 8-year follow-up.@*METHODS@#This retrospective cohort study included obese children and adolescents with a follow-up period of 8 years. Baseline clinical characteristics and DRD2 polymorphisms (including rs1076562, rs2075654, and rs4586205) were extracted from medical records. A follow-up visit was performed in May 2017 to collect related data including height, weight, diet compliance, and exercise compliance.@*RESULTS@#One hundred and nine obese children and adolescents were included in the current study. Among three DRD2 single nucleotide polymorphisms, only rs2075654 had a statistically significant association with alleviation of obesity, as the alleviation rate for minor allele carriers (68.6% for TC+TT) was higher compared to the major allele homozygote (43.3% for CC). After adjusting for all related factors, the hazard ratio of rs2075654 minor allele carriers for the alleviation of obesity was 3.34 (95% confidence interval (CI): 1.30‒8.58).@*CONCLUSIONS@#The rs2075654 polymorphism of DRD2 is related to long-term obesity alleviation in obese Chinese children and adolescents.

Association between smoking and dopamine receptor D2 polymorphisms in male patients with schizophrenia / 中国心理卫生杂志

Objective:To investigate the association between dopamine receptor D2(DRD2) polymorphisms and smoking in male patients with schizophrenia.Methods:Totally 773 patients with schizophrenia (567 smokers and 206 non-smokers) and 302 normal controls (168 smokers and 134 non-smokers) were recruited.The two single nucleotide polymorphisms (SNPs) (rs1800497 and rs1079597) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP).SHEsis genetic analysis platform was used to calculate linkage disequilibrium index and infer allele distribution and haplotype frequency.Results:There was no significant difference in two SNPs genotype and allele distributions between the patients and normal controls or between smokers and non-smokers in either patients or normal controls alone (Ps ＞ 0.05);the frequency estimations of haplotype C-A and T-G in patients with schizophrenia were higher than in normal controls (8.0％ vs.5.2％,10.2％ vs.4.1％,Ps ＜0.05),T-A (34.6％ vs.40.2％,P ＜0.05),whereas the frequency estimation of haplotype T-A in patients with schizophrenia was lower than in normal controls,and all the differences were statistically significant (34.6％ vs.40.2％,P ＜ 0.05).It was also observed that the frequency estimation of haplotype T-A in normal smokers was significantly lower than in normal non-smokers (2.5％ vs.6.1％,P ＜0.05).Conclusion:There may be a correlation between DRD2 polymorphisms and the susceptibility to schizophrenia,but not between DRD2 polymorphisms and smoking neither in patients with schizophrenia nor in normal controls.

Assessment between Dopamine Receptor D2 (DRD2) Polymorphisms and Schizophrenia in Korean Population

OBJECTIVE: The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) of dopamine receptor D2 (DRD2) are associated with schizophrenia in Korean population. METHODS: Four SNPs (rs4648317, rs7131056, rs4936270, and rs1076562) of DRD2 were selected and genotyped by direct sequencing in 197 schizophrenia patients and 370 control subjects. SNPAnalyzer, SNPStats, and Haploview version 4.2 programs were performed to analyze the genetic data. Multiple logistic regression models (codominant1, codominant2, dominant, recessive, overdominant, and log-additive) were used to evaluate the odds ratios (ORs), 95% confidence intervals (CIs), and p values. For multiple testing, p values (pc) were re-evaluated by Bonferroni's correction. RESULTS: The genotype frequency of DRD2 rs4936270 SNP was associated with the development of schizophrenia (p=0.0007, OR=1.71, 95% CI=1.16-2.52 in the codominant1 model; p=0.011, OR=1.63, 95% CI=1.12-2.37 in the dominant model; p=0.035, OR=1.41, 95% CI=1.03-1.95 in the log-additive model). The allele frequency of rs4936270 was also associated with the development of schizophrenia (p=0.024, OR=1.45, 95% CI=1.05-1.98). After Bonferroni's correction, the genotype distribution of rs4936270 was still related to the development of schizophrenia (pc=0.0028 in the codominant1 model; pc=0.044 in the dominant model). A linkage disequilibrium block consisted of rs4648317, rs7131056, and rs4936270. The CAT haplotype frequency was different between schizophrenia and controls (p=0.039). CONCLUSION: These results suggest that DRD2 SNPs may be associated with the development of schizophrenia in Korean population.