Effects of ADRB2 gene regulatory region polymorphism on the efficacy of SABA in the treatment of acute asthma attack in children / 中国药房

OBJECTIVE To explore the effects of ADRB2 gene regulatory region polymorphism on the efficacy of short-acting beta 2 receptor agonists （SABA） in the treatment of acute asthma attack in children. METHODS A total of 127 children with acute mild to moderate bronchial asthma who received SABA treatment for 7 days in the General Hospital of Northern Theater Command from October 2016 to October 2020 were selected to detect their genotype distribution and compare the improvement of pulmonary functional indicators and curative effect among different genotypes. The effect of the high-order interaction of gene polymorphism on therapeutic effect was investigated. RESULTS Among 127 children， there were 80， 44 and 3 cases of TT， TA and AA types at locus rs2895795， 93， 32 and 2 cases of CC， CG and GG types at locus rs11168070， and 41， 64 and 22 cases of GG， GA and AA types at locus rs12654778， respectively， in accordance with Hardy-Weinberg equilibrium （P＞0.05）. After treatment， the improvement rate of the peak expiratory flow in percent predicted value （PEF%pred） and the improvement rate of the forced expiratory flow at 75% vital capacity in percent predicted value （FEF75%pred） in children with TA type were significantly lower than that of TT type at locus rs2895795 （P＜0.05）； the improvement rates of PEF%pred and FEF75%pred in children with CG type were significantly lower than that of CC type at locus rs11168070 （P＜0.05）； the improvement rates of PEF%pred in children with GA and AA type were significantly lower than that of GG type at locus rs12654778 （P＜0.05）. The differences in fractional exhaled nitric oxide before and after treatment were not statistically significant among different genotypes at each locus （P＞0.05）. The proportion of remarkable improvement of children with TT type at locus rs2895795 was 2.358 times that of children with TA+ AA type （P＜0.05）， and there was no significant effect of higher-order interaction of ADRB2 polymorphism on the efficacy in children with asthma （P＞0.05）. CONCLUSIONS Polymorphisms in the regulatory region of the ADRB2 gene in children with bronchial asthma are associated with the efficacy of SABA in the treatment of acute asthma attack in children. At locus rs2895795， rs11168070 and rs12654778， the improvement of lung function of children with wild-type is more obvious， and the efficacy of SABA treatment on children with TT type is better at locus rs2895795.

Association between / 中国当代儿科杂志

OBJECTIVES@#To study the association of β2-drenergic receptor (@*METHODS@#A total of 143 children with asthma who attended the hospital from October 2016 to October 2020 were enrolled as the asthma group, among whom 61 children had mild symptoms (mild group) and 82 children had moderate-to-severe symptoms (moderate-to-severe group). A total of 137 healthy children were enrolled as the control group. Peripheral venous blood samples were collected from the two groups. The SNaPshot SNP technique was used to analyze the SNP and haplotypes of the @*RESULTS@#Polymorphisms were observed in the @*CONCLUSIONS@#SNP/haplotype of the

Study on mechanism of Tibetan medicine Zuomua Decoction in treatment of hypertension based on network pharmacology and molecular docking technology / 中国中药杂志

Hypertension is a kind of chronic cardiovascular system disease caused by a series of factors and carriers dysfunction, which belongs to the category of Tibetan medicine "Chalong disease", and has a high rate of disability and mortality. Zuomua Decoction is a classical Tibetan medicine for Chalong disease, but its mechanism is not clear. Therefore, in this paper we explored the multi-components, multi-targets and multi-channels mechanism of Zuomua Decoction in the treatment of hypertension based on network pharmacology and molecular docking technology. First of all, the chemical components of Zuomua Decoction were obtained in the retrieval of traditional Chinese medicine systems pharmacology database(TCMSP), China National Knowledge Infrastructure(CNKI) and Wanfang database. The potential targets of Zuomua Decoction were predicted by BATMAN-TCM database, and the targets of hypertension were obtained by using DisGeNET database. The intersection of these two targets set was taken to obtain the potential targets of Zuomua Decoction in the treatment of hypertension, and then the chemical compositions-targets network was constructed. Secondly, the intersection targets were imported into STRING database to obtain the interaction relationship of intersection targets, and the protein interaction network of Zuomua Decoction in the treatment of hypertension was constructed in Cytoscape. Topological, GO, and KEGG enrichment analysis were used to construct the key targets-signal pathways-biological processes network diagram and explore the mechanism of Zuomua Decoction in the treatment of hypertension. Finally, the key targets were selected to construct the pharmacodynamic identification models to verify the effect mode of Zomua Decoction in treating hypertension. The results showed that there were 61 chemical components and 90 potential targets in the compounds-targets network. We obtained 21 key targets, 154 signal pathways, and 382 biological processes in topological, GO, and KEGG enrichment analysis of the protein interaction network, and in the comprehensive analysis, it was found that Zuomua Decoction could reduce blood pressure by regulating renin angiotension aldosterone system, balancing the concentration of intracellular calcium and sodium ions and regulating vasoconstriction and relaxation. ACE, AGTR1, and ADRB2 were used as the carriers for molecular docking study on the components of Zuoma Decoction, and the results showed that the chemical components of Zuomua Decoction had a good binding activity with key targets. The purpose of this study is to provide ideas for the in-depth study of Zuoma Decoction in the treatment of hypertension, and provide scientific basis for its clinical rational application.

Effects of ADRB2（rs1042713）Gene Polymorphism on Therapeutic Efficacy of Anticholinergic Drugs in the Treatment of Refractory Asthma Pediatric Patients / 中国药房

OBJECTIVE： To study the effects of ADRB2 （rs1042713） gene polymorphism on therapeutic efficacy of anticholinergic drug in the treatment for refractory asthma pediatric patients. METHODS： 171 children with refractory asthma were selected from outpatient department of Kunming Children’s Hospital during Nov. 2016 to Jul. 2019. The distribution of ADRB2 （rs1042713） genotype， the clinical efficacy [asthma control test （C-ACT） score， FEV1， FVC， PEF， maximal mid-expiratory flow （MMEF）] of anticholinergic drug were analyzed statistically； the response of different genotypes to the use of anticholinergic drug were also analyzed statistically. RESULTS： 148 of 171 refractory asthmatics pediatric patients were administered anticholinergic drug， among them 50 of the 71 AA genotype and 36 of the 77 GA genotype responded to anticholinergic drug treatment. Statistical analysis showed that 71 children with AA refractory asthma had improved C-ACT score， FEV1， FVC， PEF and MMEF， there was statistical significance， compared with GA genotype （P＜0.05）； the response rate of the AA genotype to anticholinergic drugs was 2.71 times that of the GA genotype [OR＝2.71， 95％CI （1.38， 5.34）， P＝0.005]. CONCLUSIONS： The detection of ADRB2 （rs1042713） gene polymorphism has some guiding significance in the treatment of refractory asthma with anticholinergic drugs， and the response of AA genotype is better.

Correlation between ADRB2 gene polymorphism and childhood bronchial asthma susceptibility and drug resis-tance / 中华实用儿科临床杂志

Objective To discuss the association between ADRB2 gene polymorphism of rs1042713, rs1042714 locus and susceptibility of childhood bronchial asthma and response to the treatment,and to understant the preliminary pathogenesis of asthma preliminary. Methods The oral epithelial cells of children in asthma case group from the outpatient or inpatients at the Zhengzhou Children′s Hospital (173 cases)and healthy control group (166 ca-ses)were collec-ted. The genotypes of ADRB2 gene encoding area rs1042713 locus and rs1042714 were tested by the mean of Taqman probe real-time fluorescent quantitative PCR,and the difference was analyzed. The therapeutic effects between 2 groups were compared,and then the differences in the amino acid sequence and protein structure correspon-ding genotypes of ADRB2 genes were investigated by using bioinformatics analysis. Results There were statistical differences in genotype frequency and allele frequency of rs1042713 locus between asthma case group and healthy con-trol group(P = 0. 001,0. 000),but no difference at rs1042714 locus(P = 0. 159,0. 061). GG genotype of rs1042713 locus had significant differences in adjusting the drug dosage with AA,AG genotype patients(H = 12. 583,P = 0. 002), but the different genotype of rs1042714 locus had no significant differences in adjusting the drug dosage(H = 2. 696, P = 0. 260). The polymorphism of rs1042713 locus caused protein local structure changes,but the homologous protein structure of rs1042714 locus caused no changes. Conclusions ADRB2 gene polymorphism of rs1042713 locus is not only associated with the susceptibility of childhood bronchial asthma,but also has an effect on β2-receptor agonist treatment to a certain extent. But polymorphism of rs1042714 locus may not be associated with the susceptibility of asth-ma and the response to treatment. The reason may be different genotypes leading to different protein structures and bio-logical functions. The mechanism may be related to the structural and functional differences of protein structures corre-sponding to different genotypes.

Influence of polymorphisms of the beta-2 adrenergic receptor on the presence of exercise-induced bronchospasm in adolescents / Influência dos polimorfismos no receptor beta 2 adrenérgico na presença de broncoespasmo induzido pelo exercício em adolescentes

To determine the influence of polymorphisms of the beta-2 adrenergic receptor (ADRB2) in triggering exercise-induced bronchospasm (EIB) in adolescents. Methods: The subjects were divided into two groups: present EIB (EIB+) (n=45) and absent EIB (EIB−) (n=115). The bronchial provocation test with exercise was performed with a protocol that consisted of walking/running for at least eight minutes at high intensity, i.e., >85% of maximum heart rate, considering EIB+ as a 10% decrease in forced expiratory volume in one second (FEV1). The genotyping of the ADRB2 gene was performed by the Taqman method, using the Step One Plus system. Independent t-test, Mann–Whitney and Chi-square tests, as well as Spearman's correlation coefficient were used for the statistical analysis. Results: Age, body weight, height, FEV1, FVC and FEV1/FVC ratio were lower in the EIB+ group when compared to EIB− (p<0.05). There were no significant differences in the proportion of the allele at position 27 and Arg16Gly and Gln27Glu genotypes between the EIB+ and EIB− groups (p=0.26; p=0.97 and p=0.43, respectively). However, there was a trend toward statistical significance regarding the greater proportion of the Gly16 allele for the EIB+ when compared to the EIB− group (p=0.08). Conclusions: The presence of polymorphisms associated with the Glu27 allele and Arg16Gly and Gln27Glu genotypes had no influence on EIB. However, the statistical trend toward greater frequency of the Gly16 allele in individuals with EIB+ can be considered evidence of the influence of polymorphisms of the ADBR2 gene on EIB in adolescents.

Determinar a influência dos polimorfismos dos receptores adrenérgicos beta 2 (ADRB2) no desencadeamento de broncoespasmo induzido pelo exercício (BIE) em adolescentes. Métodos: Os sujeitos foram divididos em dois grupos: BIE presente (BIE+) (n=45) e BIE ausente (BIE−) (n=115). O teste de broncoprovocação com exercício foi feito com protocolo que consistiu em caminhar/correr durante no mínimo oito minutos em intensidade superior a 85% da frequência cardíaca máxima, considerando como BIE presente uma queda de 10% do volume expiratório forçado no primeiro segundo (VEF1). A genotipagem do gene ADRB2 foi feita pelo método Taqman por meio do aparelho Step One Plus. Para análise estatística usaram-se os testes t independente, U de Mann-Whitney, qui-quadrado e coeficiente de correlação de Spearman. Resultados: Idade, massa corporal, estatura, VEF1, CVF e relação VEF1/CVF foram menores no grupo BIE+ em comparação com o BIE− (p<0,05). Não houve diferenças significativas na proporção do alelo na posição 27 e dos genótipos Arg16Gly e Gln27Glu entre os grupos BIE+ e BIE− (p=0,26; p=0,97 e p=0,43, respectivamente). Entretanto, verificou-se uma tendência à significância estatística na maior proporção do alelo Gly16 para o grupo BIE+ comparado com o BIE− (p=0,08). Conclusões: A presença de polimorfismos associados ao alelo Glu27 e os genótipos Arg16Gly e Gln27Glu não influenciam no BIE. Porém, a tendência estatística observada para uma maior frequência do alelo Gly16 nos indivíduos com a presença de BIE pode ser considerado indício da influência de polimorfismos no gene ADBR2 no BIE em adolescentes.

Thyrotoxic Periodic Paralysis and Polymorphisms of the ADRB2, AR, and GABRA3 Genes in Men with Graves Disease

BACKGROUND: Thyrotoxic periodic paralysis (TPP) is a rare complication of thyrotoxicosis characterized by acute attacks of muscle weakness and hypokalemia. Recently, variation in several genes was suggested to be associated with TPP. This study evaluated the genetic predisposition to TPP in terms of the β2-adrenergic receptor (ADRB2), androgen receptor (AR), and γ-aminobutyric acid receptor α3 subunit (GABRA3) genes. METHODS: This study enrolled 48 men with Graves disease (GD) and TPP, and 48 GD patients without TPP. We compared the frequencies of candidate polymorphisms between the two groups. RESULTS: The frequency of the Gly16/Gly16 genotype in ADRB2 was not significantly associated with TPP (P=0.32). More CAG repeats (≥26) in the AR gene were not correlated with TPP (odds ratio [OR], 2.46; 95% confidence interval [CI], 0.81 to 8.09; P=0.08). The allele frequency of the TT genotype in the GABRA3 gene was not associated with TPP (OR, 1.83; 95% CI, 0.54 to 6.74; P=0.41). CONCLUSION: The polymorphisms in the ADRB2, AR, and GABRA3 genes could not explain the genetic susceptibility to TPP in Korean men with GD.

Beta 2-adrenergic receptor gene association with overweight and asthma in children and adolescents and its relationship with physical fitness / Associação do gene ADRB2 com sobrepeso e asma em crianças e adolescentes e sua relação com a aptidão física

Objective: To investigate the association of Arg16Gly and Gln27Glu polymorphisms of β2-adrenergic receptor gene (ADRB2) with the occurrence of asthma and overweight and the gene's influence on anthropometric, clinic, biochemical and physical fitness variables in children and adolescents. Methods: Subjects were evaluated for allelic frequencies of the β2-adrenergic receptor gene, height, weight, body mass index (BMI), BMI Z-score, waist circumference (WC), pubertal stage, resting heart rate (HRres), blood pressure (BP), total cholesterol (TC), glucose, insulin, high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), triglyceride (TG), Homeostasis Metabolic Assessment (HOMA2-IR), Quantitative Insulin Sensitivity Check Index (QUICKI) and maximal oxygen uptake (VO2max). The participants were divided in four groups: overweight asthmatic (n=39), overweight non-asthmatic (n=115), normal weight asthmatic (n=12), and normal weight non-asthmatic (n=40). Results: Regarding the Gln27Glu polymorphism, higher total cholesterol was observed in usual genotype individuals than in genetic variant carriers (p=0.04). No evidence was found that the evaluated polymorphisms are influencing the physical fitness. The Arg16 allele was found more frequently among the normal weight asthmatic group when compared to the normal weight non-asthmatic group (p=0.02), and the Glu27 allele was more frequently found in the overweight asthmatics group when compared to the normal weight non-asthmatic group (p=0.03). Conclusions: The association of Arg16 allele with the occurrence of asthma and of the Glu27 allele with overweight asthmatic adolescents evidenced the contribution of the β2-adrenergic receptor gene to the development of obesity and asthma.

Objetivo: Investigar a associação dos polimorfismos Arg16Gly e Gln27Glu do gene receptor β2-adrenérgico (ADRB2) com a ocorrência de asma e sobrepeso, bem como a influência do gene sobre variáveis antropométricas, clínicas, bioquímicas e de aptidão física em crianças e adolescentes. Métodos: Os indivíduos foram avaliados quanto à frequência alélica do gene ADRB2, estatura, peso, índice de massa corporal, IMC-escore Z, circunferência abdominal, estágio puberal, frequência cardíaca de repouso, pressão arterial, colesterol total, glicose, insulina, lipoproteína de alta densidade, lipoproteína de baixa densidade, triglicerídeos, Homeostasis Metabolic Assessment (HOMA2-IR), Quantitative Insulin Sensitivity Check Index (QUICKI) e consumo máximo de oxigênio (VO2max). Os participantes foram divididos em quatro grupos: sobrepeso asmático (n=39), sobrepeso não asmático (n=115), peso normal asmático (n=12) e peso normal não asmático (n=40). Resultados: Com relação ao polimorfismo Gln27Glu, foi observado maior valor de colesterol total nos indivíduos do genótipo usual do que naqueles que carregam a variante (p=0,04). Não foi encontrada evidência de que os polimorfismos avaliados influenciem a aptidão física. O alelo Arg16 foi encontrado em maior frequência no grupo de peso normal asmático comparado com o grupo de peso normal não asmático (p=0,02) e o alelo Glu27 foi mais frequentemente encontrado no grupo de sobrepeso asmático comparado com o grupo de peso normal não asmático (p=0,03). Conclusões: A associação do alelo Arg16 com a ocorrência de asma e a associação do alelo Glu27 com adolescentes com sobrepeso asmáticos evidenciam a contribuição do gene ADBR2 para o desenvolvimento da obesidade e da asma.

Association between ADRB2 rs1042713 gene polymorphism and susceptibility of asthma in Chinese Population:a meta-analysis / 中国免疫学杂志

Objective:To investigate the association between rs1042713 polymorphisms of ADRB2 gene and the susceptibility of asthma in Chinese Population by meta-analysis.Methods: The Pubmed database,Emabase database,Web of Knowledge database, CNKI database,Wanfang database and Weipu database were searched for all publications about the susceptibility of asthma and the rs1042713 polymorphisms of ADRB2 gene in Chinese Population.The article which met the inclusion criteria were assessed by the STA-TA12.0 software.Results:12 studies were included,with 2 193 asthmatic patients and 2 033 controls.All the included articles were satisfied to the Hardy-Weinberg equilibrium.The results of Meta-analysis was showed that the risk of asthma of the mutations G carriers ( GG +GA) on ADRB2 gene rs1042713 loci in Chinese people compared with the wild-type homozygotes( AA) was not significantly in-creased overall(OR=1.08,95% CI=0.82-1.44).However,subgroup analysis showed that the risk of G carriers of children had a relatively higher incidence(OR=1.69,95% CI 0.99-2.87),while the risk of adult-onset have a relatively lower incidence(OR=0.88,95%CI 0.68-1.15).Conclusion:The ADRB2 gene rs1042713 polymorphisms have a certain correlation with the susceptibility of asthma in Chinese children,the mutant gene G carriers may relatively increase the risk of asthma in childhood.

Preliminary study on association of β2 - Adrenergic Receptor Polymorphism with hypertension in hypertensive subjects attending Balok Health Centre, Kuantan

Polymorphisms within the β2-adrenergic receptor (ADRB2) gene have been repeatedly linked to hypertension. Among the ADRB2 polymorphisms detected, Arg16Gly and Gln27Glu codons are considered the two most important variations. The amino acid substitution at these codons may lead to abnormal regulation of ADRB2 activity. The aim of the present study was to assess the association between ADRB2 polymorphisms and hypertension. This case-control study consisted of 100 unrelated subjects (50 hypertensive and 50 matched normal controls). Arg16Gly and the Gln27Glu polymorphisms were analyzed by polymerase chain reactionrestriction fragment length polymorphism assay. There were no significant evidence of association in allelic and genotypes distribution of Arg16Gly and Glu27Gln with blood pressure and hypertension. These findings suggest that the variation within codon 16 and 27 of ADRB2 gene were unlikely to confer genetic susceptibility for hypertension in our population samples.

Association of beta2-Adrenergic Receptor Polymorphism with Work-Related Symptoms in Workers Exposed to Wheat Flour

PURPOSE: Our previous study indicated that the presence of wheat-specific IgG1 and IgG4 antibodies was associated with work-related symptoms in workers exposed to wheat flour. We performed this study to investigate the genetic polymorphisms of beta2-adrenergic receptors and wheat-specific antibodies in association with the clinical parameters of baker's asthma. MATERIALS AND METHODS: In total, 379 subjects working in a single industrial bakery were enrolled in this study. The skin prick test was performed with common inhalant allergens and wheat flour extract. The presence of serum- specific IgE, IgG1, and IgG4 antibodies to wheat flour were determined by ELISA. Whole blood samples were obtained for genotype analysis. Subjects were genotyped with regard to five candidate single nucleotide polymorphisms (SNPs) of the beta2-adrenergic receptor gene (ADRB2; -47 T>C, 46 A>G, 79 C>G, 252 G>A, and 523 C>A) using a single-base extension method. RESULTS: No significant associations were observed between the genotype/allele frequencies of any of the SNPs tested and any clinical parameters. The haplotype of ADRB2 (GAA composed of 46 A>G, 252 G>A, and 523 C>A) was significantly associated with work-related symptoms (pG and haplotype [GAA] of ADRB2, the prevalence rates of wheat-specific IgG1 antibodies and lower respiratory symptoms increased significantly with exposure intensity (both p<0.05). CONCLUSION: The findings of the present study suggest that ADRB2 genetic polymorphism may contribute to the development of work-related symptoms in workers exposed to wheat flour, which can lead to baker's asthma.

Association of beta2-Adrenergic Receptor Polymorphism with the Phenotype of Aspirin-Intolerant Acute Urticaria

The genetic mechanism of aspirin intolerant acute urticaria (AIAU) is unknown. To demonstrate an association between the beta2 adrenergic receptor (ADRB2) polymorphism and the phenotype of AIAU, one hundred fourteen patients with AIAU, 110 patients with aspirin intolerant chronic urticaria (AICU), and 498 normal healthy controls (NC) based on a Korean population were enrolled. The genotype of ADRB2 at 46 A > G was analyzed using a direct sequencing method. The ADRB2 polymorphism at 46 A > G showed a significant difference between AIAU and NC; the frequency of the major genotype was significantly higher in the AIAU group (p= 0.017 in recessive model), while no differences were noted in allele and genotype frequencies between AICU and NC. In conclusion, the ADRB2 (46 A > G) gene polymorphism may contribute to the development of the phenotype of AIAU.