OBJECTIVE: To explore the association between rs2587552 polymorphism (has a strong lin-kage disequilibrium with rs1800497 which had been found in many studies to be related to obesity, r²=0.85) of DRD2 gene and the effect of a childhood obesity intervention in Chinese population, and provide a scientific basis for future personalized childhood obesity intervention based on genetic background. METHODS: From a multi-center cluster randomized controlled trial studying the effect of a childhood obesity intervention, we enrolled 382 children from 8 primary schools (192 and 190 children from intervention and control groups, respectively) in Beijing as study subjects. Saliva was collected and DNA was extracted to detect the rs2587552 polymorphism of DRD2 gene, and the interactions between the gene and study arms on childhood obesity indicators [including body weight, body mass index (BMI), BMI Z-score, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio, and body fat percentage] were analyzed. RESULTS: No association was found between rs2587552 polymorphism and the changes in hip circumference or body fat percentage in the intervention group (P>0.05). However, in the control group, children carrying the A allele at DRD2 rs2587552 locus showed a greater increase in hip circumference and body fat percentage compared with those not carrying A allele (P < 0.001). There were interactions between rs2587552 polymorphism of DRD2 gene and study arms on the changes in hip circumference and body fat percentage (P=0.007 and 0.015, respectively). Compared with the control group, children in the intervention group carrying the A allele at DRD2 rs2587552 locus showed decrease in hip circumference by (-1.30 cm, 95%CI: -2.25 to -0.35, P=0.007) and decrease in body fat percentage by (-1.34%, 95%CI: -2.42 to -0.27, P=0.015) compared with those not carrying A allele. The results were consistent between the dominant model and the additive model (hip circumfe-rence: -0.66 cm, 95%CI: -1.28 to -0.03, P=0.041; body fat percentage: -0.69%, 95%CI: -1.40 to 0.02, P=0.056). No interaction was found between rs2587552 polymorphism and study arms on the changes in other childhood obesity-related indicators (P>0.05). CONCLUSION Children carrying the A allele at rs2587552 polymorphism of DRD2 gene are more sensitive to intervention and showed more improvement in hip circumference and body fat percentage after the intervention, suggesting that future personalized childhood obesity lifestyle intervention can be carried out based on the rs2587552 polymorphism of DRD2 gene.
Humans ; Child ; Pediatric Obesity/therapy* ; Prospective Studies ; Polymorphism, Genetic ; Body Mass Index ; Waist Circumference ; Receptors, Dopamine D2/genetics*

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.
Adolescent ; Body Mass Index ; Child ; Female ; Humans ; Male ; Obesity/genetics* ; Polymorphism, Single Nucleotide ; Receptors, Dopamine D2/genetics* ; Retrospective Studies

Objective: To investigate the association between three single nucleotide polymorphism (SNP) genes DRD2 (rs1800497, rs6275, and rs1799978) and the dosage used on methadone maintenance treatment (MMT). Methods: From the methadone maintenance treatment centers, 257 MMT patients were recruited to participate in a case-control study and divided into two groups-control groups under low dosage (n=89) and case (n=168) group with high dosage. Quanto software was used to estimate the sample size as 180. Information related to social-demographic status, history on drug use and medication were collected. And DRD2 SNPs were genotyped to explore the relationship between polymorphism of DRD2 gene and the dosage of methadone maintenance treatment. Results: Distributions of DRD2 rs6275 between different groups were significantly different. Patients carrying TC genotype needed lower dose of methadone when compared to the patients that carrying CC genotype counterparts (OR=0.338, 95% CI: 0.115-0.986). Patients that carrying C allele at rs6275 needed lower methadone dose than those that carrying genotype TT (OR=0.352, 95% CI: 0.127-0.975). Distributions of genotypes, alles in the other two SNPs (rs1800497, rs1799978) were not significantly different between groups under different dosages. Conclusion: DRD2 rs6275 was associated with dosage of methadone used for the MMT patients. However, no significant associations were found between rs1800497, rs1799978 and the dosage of methadone.
Alleles ; Case-Control Studies ; Drug Dosage Calculations ; Genotype ; Humans ; Methadone/therapeutic use* ; Opiate Substitution Treatment ; Opioid-Related Disorders/rehabilitation* ; Polymorphism, Single Nucleotide/genetics* ; Receptors, Dopamine D2/genetics*

OBJECTIVETo study the effects of rs4274224 polymorphisms in the DRD2 gene, family factors and their interaction on the regularity in school-age children.

METHODSThe rs4274224 polymorphisms were genotyped using Sequenom Mass Array. The regularity was assessed based on the Middle Childhood Temperament Questionnaire (MCTQ). The parental rearing pattern was assessed with Egna Minnen av Bardnodnauppforstran (EMBU). The family function was assessed using Family Cohesion and Adaptability Scale (FACES II-CV).

RESULTSThe regularity score in children with AA genotype of rs4274224 in the DRD2 gene was significantly lower than in those with GA/GG genotype (2.9±0.6 vs 3.1±0.7; P<0.05). The results of multiple regression analysis showed that the regularity was related to child gender, father's education level and family adaptability. The results of logistic regression analysis showed that the main factors influencing the regularity were family adaptability and its interaction with rs4274224 polymorphisms. The regularity was better in children with high family adaptability than in those with low family adaptability (OR=0.112, P<0.01). The children with AA genotype and low family adaptability were tend to be associated with low regularity (OR=21.554, P<0.01).

CONCLUSIONSThe regularity based the temperament for school-age children might be influenced by family adaptability and its interaction with rs4274224 polymorphisms.

Child ; Female ; Genotype ; Humans ; Male ; Polymorphism, Genetic ; Receptors, Dopamine D2 ; genetics ; Surveys and Questionnaires ; Temperament

OBJECTIVETo investigate the mRNA expression of dopamine receptor D2 (DRD2) and dopamine transporter (DAT) in peripheral blood lymphocytes before and after treatment in children with tic disorder (TD).

METHODSRT-PCR was used to measure the mRNA expression of DRD2 and DAT in peripheral blood lymphocytes before and after treatment in 60 children with TD. The correlations between mRNA expression of DRD2 and DAT and the severity of TD were analyzed. Sixty healthy children served as the control group.

RESULTSBefore treatment, the children with TD had a significant increase in the mRNA expression of DRD2 and DAT compared with the control group (P<0.05). After 3 months of treatment with oral aripiprazole, the mRNA expression of DRD2 decreased significantly (P<0.05), while that of DAT showed no significant changes in children with TD. In the children with moderate or severe TD, the mRNA expression of DRD2 was positively correlated with Yale Global Tic Severity Scale (YGTSS) score (P<0.05). In the children with moderate TD, the mRNA expression of DAT was positively correlated with YGTSS score (P<0.05).

CONCLUSIONSIn children with TD, the mRNA expression of DRD2 in peripheral blood lymphocytes can be used as one of the indicators for diagnosing TD, assessing the severity of TD, and evaluating clinical outcomes.

Adolescent ; Child ; Child, Preschool ; Dopamine Plasma Membrane Transport Proteins ; genetics ; Female ; Humans ; Lymphocytes ; metabolism ; Male ; RNA, Messenger ; blood ; Receptors, Dopamine D2 ; genetics ; Tic Disorders ; drug therapy ; metabolism ; mortality

OBJECTIVETo study the association between rs1079595 polymorphisms in the DRD2 gene and the distractibility in school-age children.

METHODSThe genotyping at rs1079595 was performed and the distractibility was measured based on the temperament questionnaire in 120 8-12 years old school-age children in order to analyze the effects of the rs1079595 polymorphism and its interaction with the gender, age and delivery mode on the distractibility.

RESULTSThere was an association between the distractibility and rs1079595 polymorphisms. The distractibility score in children with GG/GT genotypes was significantly higher than in children with the TT genotype (4.3 ± 0.6 vs 4.0 ± 0.7; P<0.05). The interaction between rs1079595 polymorphisms and the delivery mode produced an effect on the distractibility. The normal delivery children with T alleles were associated with a low distractibility (OR=0.037, P<0.01).

CONCLUSIONSThe distractibility based the temperament might be influenced by the rs1079595 polymorphism and its interaction with the delivery mode in school-age children.

Child ; Delivery, Obstetric ; Female ; Genotype ; Humans ; Logistic Models ; Male ; Polymorphism, Genetic ; Receptors, Dopamine D2 ; genetics ; Temperament

OBJECTIVE: To evaluate the association between D2 dopamine receptor gene -141C Ins/Del polymorphism and heroin dependence in Chinese Han population. METHODS: Chinese and foreign databases were searched for relevant articles published from the establishment of database to March 2014. Case-control studies on D2 dopamine receptor gene -141C Ins/Del polymorphism with heroin dependence in Chinese Han population were gathered with Meta-analysis by Stata 12.0 software after data abstraction. RESULTS: Seven case-control studies on association between D2 dopamine receptor gene -141C Ins/ Del polymorphism and heroin dependence were included, which covered 3 211 heroin dependence patients and 1 979 controls. Meta-analysis results showed that the pooled odds ratio (OR), the 95% confidence interval (CI) and P value after combining genotypes were as follows: Ins/Ins vs Del/Del: OR=0.51, 95% CI: 0.27-0.96, P=0.017; Ins/Ins vs Ins/Del+Del/Del: OR=0.82, 95% CI: 0.72-0.94, P=0.448; Ins/Ins+ Ins/Del vs Del/Del: OR=0.53, 95% CI: 0.28-0.98, P=0.019; Ins/Del vs Del/Del: OR=0.59, 95% CI: 0.32-1.07, P=0.045; Ins vs Del: OR=0.79, 95% CI: 0.71-0.89, P=0.101). CONCLUSION D2 dopamine receptor gene -141C Ins/Del polymorphism is associated with heroin dependence in Chinese Han population, and Chinese Han population with Ins allele gene deletion are at lower risk of heroin dependence.
Alleles ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Genotype ; Heroin Dependence ; genetics ; Humans ; INDEL Mutation ; Polymorphism, Genetic ; Receptors, Dopamine D2 ; genetics

OBJECTIVETo study and compare the effect of Corydalis yanhusuo and L-THP on dopamine neurotransmitter and D2 receptor of reward circuitry in various cerebral areas of conditioned place preference model rats and the comparison of their effects.

METHODThe CPP model was established by injecting morphine in rats with increasing doses for 10 days. The initial dose of 10 mg x kg(-1), and the final dose of 100 mg x kg(-1), with 10 mg x kg(-1) increased each day. At 48 h after the final training, CPP was adopted to detect the successful establishment of the model. On the same day (12 d), they were orally administered with 2, 1, 0.5 g x kg(-1) C. yanhusuo (containing 0.153, 0.077 and 0.038 mg L-THP) and L-THP (3.76, 1.88, 0.94 mg x kg(-1)) for six days. On 18 d, CPP test was performed again. Next day, HPLC was adopted to determine the content of dopamine neurotransmitters of reward circuitry in VTA-NAc-PFC; Immunohistochemistry and Western blotting were adopted to detect the expression of D2 receptors.

RESULTCompared with the physiological saline treatment group, C. yanhusuo (2, 1 g x kg(-1)) and L-THP (3.76, 1.88 mg x kg(-1)) groups showed that rats stayed in a notably shorter period in white boxes (morphine-accompanied boxes) (P < 0.01 or P < 0.05), and revealed a remarkably lower dopamine content in VTA, NAc and PFC and the significant increase in the expression of D2 receptor (P < 0.01 or P < 0.05).

CONCLUSIONThe down-regulation of the increased dopamine content in reward nervous circuitry and the up-regulation of the expression of D2 receptor may be one of mechanisms of C. yanhusuo and L-THP in accelerating the recession of morphine's CPP effect Regarding the inhibition of morphine's CPP effect and the effect on dopamine system, the effect of C. yanhusuo traditional Chinese medicine containing one-fold L-THP monomer is equal to that of the independent application of around 24-fold L-THP monomer.

Animals ; Berberine Alkaloids ; administration & dosage ; Brain ; drug effects ; metabolism ; physiopathology ; Conditioning, Operant ; drug effects ; Corydalis ; chemistry ; Dopamine ; metabolism ; Humans ; Male ; Morphine ; adverse effects ; Plant Extracts ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine D2 ; genetics ; metabolism ; Substance-Related Disorders ; drug therapy ; genetics ; metabolism ; psychology

OBJECTIVETo investigate whether there is an association between DRD2/ANKK1 Taq IA polymorphism and early infant temperament.

METHODSDRD2/ANKK1 Taq IA polymorphism (rs1800497) was determined using polymerase chain reaction-ligase detection reaction (PCR-LDR) techniques in 149 Chinese Han infants from Changsha City. Their mothers were asked to complete the Early Infant Temperament Questionnaires (EITQ) when the infants were 1 to 4 months old (mean: 2.75 months). There were three genotypes found in these infants: C/C, T/T and C/T. The subjects were subdivided into T-carrier (CT, TT) and non-T-carrier (CC) groups for statistical analysis.

RESULTSThere were no differences in the temperament style distribution between the T-carrier and non-T carrier groups. There were also no statistically significant differences between the two groups in the score of the nine temperament dimensions.

CONCLUSIONSDRD2/ANKK1 Taq IA polymorphism is not associated with early infant temperament.

Genotype ; Humans ; Infant ; Polymorphism, Genetic ; Protein-Serine-Threonine Kinases ; genetics ; Receptors, Dopamine D2 ; genetics ; Temperament

OBJECTIVETo evaluate the effect of Qufeng Zhidong Recipe (QZR) on the head tic behavior, and the mRNA expressions of Notch1 and dopamine D2 receptor (D2R) in tic disordered mice.

METHODSMouse model like wet-dog shake head tic disorder was established by peritoneal injection of 5-HT2A/C agonist DOI for 14 successive days. The model mice were divided into three groups, the model group, the Chinese medicine (CM) treated group and the Western medicine (WM) treated group, they were intervened respectively with distilled water, QZR (10 g/kg) and haloperidol (1 mg/kg). Besides, a normal control group was set up and gastrogavaged with distilled water. The effect of intervention was evaluated 2 weeks later by estimating the head tic and the creeping distance of animals, and the mRNA expressions of D2R and Notch1 in corpus striatum and prefrontal cortex regions were detected using Real-time PCR.

RESULTSThe wet-dog shake response and the creeping distance of mice were significantly reduced after intervention in both intervened groups, showing insignificant difference between the effects of CM and WM (P > 0.05). The expression of D2R mRNA in corpus striatum was higher than that in the prefrontal cortex (P < 0.01), at the prefrontal cortex, it was 151 +/- 30 in the CM group and 180 +/- 41 in the WM group, and at the corpus striatum, 710 +/- 64 and 850 +/- 80 respectively, all higher than those in the model group (P < 0.05). While the Notch1 mRNA expression in model mice were lower at the prefrontal cortex than at the corpus striatum (P < 0.05). After intervention it was 55 +/- 20 in the CM group and 48 +/- 23 in the WM group at the prefrontal cortex, all significantly lower than that in the model group (P < 0.05).

CONCLUSIONDOI-induced wet-dog shake response could well simulate the clinical characteristics of tic disorder; QZR could improve the tic behavior and creeping distance in the model mice. The up-regulation of D2R mRNA expression after QZR intervention may be related with the down-regulation of Notch1 expression, this findings is worthy of further studies.

Animals ; Corpus Striatum ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Phytotherapy ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Receptor, Notch1 ; genetics ; metabolism ; Receptors, Dopamine D2 ; genetics ; metabolism ; Signal Transduction ; drug effects ; Tic Disorders ; drug therapy