P51 - ADRB2 gene polymorphisms of the asthma pediatric patients in Russia’s Perm region
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ABSTRACT:
SUBMITTER: Furman E
PROVIDER: S-EPMC4082047 | biostudies-literature | 2014 Jan
REPOSITORIES: biostudies-literature
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Project description:ObjectivesTo study the association of β2-drenergic receptor (ADRB2) regulatory region single nucleotides polymorphism (SNP)/haplotypes at rs11168070, rs17108803, rs2053044, rs12654778, rs11959427, and rs2895795 loci with childhood asthma.MethodsA 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 ADRB2 regulatory region at rs11168070, rs17108803, rs2053044, rs12654778, rs11959427, and rs2895795 loci in all children. The asthma group and the control group were compared in terms of the association of ADRB2 regulatory region SNP and haplotypes at the above six loci with susceptibility to asthma and severity of asthma.ResultsPolymorphisms were observed in the ADRB2 regulation region at the above six loci in both the asthma group and the control group, with significant differences between the two groups in the distribution of genotype and allele frequencies at rs2895795 (-1429T /A), rs2053044(-1023G/A), and rs12654778 (-654G/A) loci (P<0.05). Linkage disequilibrium of SNP was observed at the six loci of the ADRB2 regulatory region.The haplotypes of TATGCT, TATGGC, and AGTGCT were associated with susceptibility to childhood asthma, among which TATGCT and TATGGC were risk factors for childhood asthma (OR=1.792 and 1.946 respectively, P<0.05), while AGTGCT was a protective factor (OR=0.523, P<0.05).ConclusionsSNP/haplotype of the ADRB2 regulatory region is associated with the susceptibility to childhood asthma. The haplotypes of TATGCT and TATGGC formed by such SNP/haplotype are risk factors for childhood asthma, while AGTGCT is a protective factor.
| S-EPMC8580024 | biostudies-literature
Project description:Inhaled β2 adrenergic receptor (β2-AR) agonists are the mainstay of asthma therapy. The β2-AR protein is encoded by the ADRB2 gene and variants within this gene can have significant consequences for modulating the response to asthma therapy. This cross-sectional study performed at the University Children's Hospital in Belgrade, included 54 children with asthma. The subjects were genotyped for ADRB2 +46A>G (Arg16Gly, rs1042713) and +79C>G (Gln27Glu, rs 1042714) polymorphisms and the association with asthma severity and response to inhaled salbutamol was examined. In Serbian asthmatic children, allele +46A was detected with a frequency of 41.7% and allele +79G was detected with a frequency of 23.1%. Allele +46G was found to be associated with a better response to inhaled salbutamol (p <0.05) and with mild form of asthma (p <0.05). Polymorphism ADRB2 +46A>G may be a determinant of asthma severity and response to salbutamol in children with asthma. We did not find any association of +79C>G polymorphisms with the asthma severity and bronchodilator response to inhaled salbutamol. The results of this study can be potentially useful for personalization of asthma treatment.
| S-EPMC6231319 | biostudies-literature
Project description:Background and objectiveA number of studies have assessed the relationship between beta-2 adrenergic receptor (ADRB2) gene polymorphisms and asthma risk. However, the results are inconsistent. A meta-analysis that focused on the association between asthma and all ADRB2 polymorphisms with at least three case-control studies was thus performed.MethodsA literature search of the PubMed, Embase, Web of Science, CNKI, and Wangfang databases was conducted. Odds ratios with 95% confidence intervals were used to assess the strength of associations.ResultsArg16Gly, Gln27Glu, Thr164Ile, and Arg19Cys single nucleotide polymorphisms (SNPs) were identified in 46 case-control studies. The results showed that not all of the SNPs were associated with asthma in the overall population. Significant associations were found for the Arg16Gly polymorphism in the South American population via dominant model comparison (OR = 1.754, 95% CI = 1.179-2.609, I2 = 16.9%, studies = 2, case = 314, control = 237) in an analysis stratified by ethnicity. For the Gln27Glu polymorphism, a protective association was found in children via recessive model comparison (OR = 0.566, 95% CI = 0.417-0.769, I2 = 0.0%, studies = 11, case = 1693, control = 502) and homozygote genotype comparison (OR = 0.610, 95% CI = 0.434-0.856, I2 = 0.0%, studies = 11, case = 1693, control = 1502), and in adults via dominant model comparison (OR = 0.864, 95% CI = 0.768-0.971, I2 = 46.9%, n = 18, case = 3160, control = 3433).ConclusionsNone of the ADRB2 gene polymorphisms were reproducibly associated with a risk of asthma across ethnic groups in the general population.
| S-EPMC4128804 | biostudies-literature
Project description:Asthma is the leading chronic disease in children. Several studies have identified genetic biomarkers associated with susceptibility and severity in both adult and pediatric cases. In this study, we evaluated outcomes in 400 African American and European American pediatric cases all of whom were regular users of inhaled corticosteroids. Patients were stratified by genotype using two single nucleotide polymorphisms in the β-2-adrenergic receptor (ADRB2) gene - rs1042713 and rs1042714, previously associated with asthma outcome. These correspond to nonsynonymous single nucleotide polymorphisms at positions 16 [arginine to glycine (Arg16Gly); rs1042713] and 27 [glutamic acid to glutamine (Glu27Gln); rs1042714], which are relatively common (minor allele frequencies ∼40-50%), and have been well characterized in asthma pharmacogenetics. We controlled for adherence to the National Heart, Lung and Blood Institute guidelines using deep mining of electronic health record data to determine treatment course. We found no significant effect for rs1042713 (Arg16Gly) but did identify an effect for rs1042714, where participants homozygous for Gln27 had increased exacerbations while taking inhaled corticosteroids in comparison with those who were either heterozygous or homozygous for Glu27. This is consistent with previous studies and demonstrates for the first time that the Glu27 variant in the ADRB2 gene is associated with increased frequencies of asthma exacerbations. Moreover, this study also lends an important proof-of-principle on how electronic health records linked to genotype can be efficiently and systematically mined to delineate health outcomes.
| S-EPMC6417505 | biostudies-literature
Project description:BackgroundEvidence suggests that variation in the length of the poly-C repeat in the 3' untranslated region (3'UTR) of the β2-adrenergic receptor gene (ADRB2) may contribute to interindividual variation in β-agonist response. However, methodology in previous studies limited the assessment of the effect of sequence variation in the context of poly-C repeat length. The objectives of this study were to design a novel genotyping method to fully characterize sequence variation in the ADRB2 3'UTR poly-C repeat in asthma patients treated with inhaled corticosteroid and long-acting β2-adrenergic agonist (ICS/LABA) combination therapy, and to analyze the effect of the poly-C repeat polymorphism on clinical response.MethodsIn 2,250 asthma patients randomized to treatment with budesonide/formoterol or fluticasone/salmeterol in a six-month study (AstraZeneca study code: SD-039-0735), sequence diversity in the ADRB2 poly-C repeat region was determined using a novel sequencing-based genotyping method. The relationship between the poly-C repeat polymorphism and the incidence of severe asthma exacerbations, and changes in pulmonary function and asthma symptoms from baseline to the average during the treatment period, were analyzed.ResultsPoly-C repeat genotypes were assigned in 97% (2,192/2,250) of patients. Of the 13 different poly-C repeat alleles identified, six alleles occurred at a frequency of >5% in one or more population in this study. The repeat length of these six common alleles ranged from 10 to 14 nucleotides. Twelve poly-C repeat genotypes were observed at a frequency of >1%. No evidence of an association between poly-C repeat genotype and the incidence of severe asthma exacerbations was observed. Patients' pulmonary function measurements improved and asthma symptoms declined when treated with ICS/LABA combination therapy regardless of poly-C repeat genotype.ConclusionsThe extensive sequence diversity present in the poly-C repeat region of the ADRB2 3'UTR did not predict therapeutic response to ICS/LABA therapy.
| S-EPMC3441247 | biostudies-literature
Project description:BACKGROUND The ADRB2 gene encodes the ß2-adrenergic receptor (ß2-AR). This study aimed to determine the association between the C79G polymorphism of the ADRB2 gene and its association with pediatric asthma using a meta-analysis of the published data. MATERIAL AND METHODS Review of publications up to May 2018 was from the PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and WanFang databases. The odds ratio (ORs) with 95% confidence interval (CI) were used in evaluating the strength of the reported association between the C79G polymorphism of the ADRB2 gene and pediatric asthma. RESULTS There were 18 controlled studies that included 2,982 pediatric cases of asthma and 2,651 controls. Expression of the C79G polymorphism of the ADRB2 gene was significantly associated with risk of pediatric asthma associated with the C or G allele with comparison of the co-dominant model (GG vs. CC: OR, 0.69; 95% CI, 0.55-0.88) and the recessive model (GG vs. CC+CG: OR, 0.65; 95% CI, 0.53-0.81). Subgroup analysis by ethnicity showed a significantly reduced risk of pediatric asthma in Asian patients for comparison of the co-dominant model (GG vs. CC: OR, 0.59; 95% CI, 0.45-0.78), the recessive model (GG vs. CC+CG: OR, 0.58; 95% CI, 0.45-0.76), and the allelic model (G vs. C: OR, 0.89; 95% CI, 0.79-0.99). CONCLUSIONS The C79G polymorphism of the ADRB2 gene encoding ß2-AR was associated with a reduced risk for the development of pediatric asthma, particularly in the Asian population.
| S-EPMC6559004 | biostudies-literature
Project description:Gut microbiota are closely related to health, and the β2-adrenergic receptor (ADRB2) gene is associated with gastrointestinal diseases. However, little is known about the relationship between ADRB2 gene polymorphisms and intestinal microbiota. In the present study, we aimed to explore the relationship between ADRB2 gene polymorphisms and gut microbiota in Chinese Han adolescents. Data analysis showed that the relative abundance, PICRUSt function prediction, and Chao1 and ACE indices of gut microbiota were significantly different between males and females (P < 0.05). The rs1042711 was positively associated with the relative abundance of Actinobacteria, Coriobacteriia, Bifidobacteriales, Erysipelotrichi, and Erysipelotrichales. The rs12654778 was negatively associated with Bacilli, Lactobacillales, Bacteroidaceae, and Bacteroides. rs1042713 was positively associated with Lactobacillales and Bifidobacteriales. The rs1042717 was positively associated with Bifidobacteriales and negatively associated with Veillonellaceae. The rs1042719 was negatively associated with Erysipelotrichi and Erysipelotrichales and positively associated with Erysipelotrichi, Erysipelotrichales, Bifidobacteriales, and Ruminococcaceae in females. The rs1801704 was positively associated with Erysipelotrichi, Erysipelotrichales, Bifidobacteriales, Actinobacteria, Coriobacteriia, and Bifidobacteriales. The rs2053044 was positively associated with Ruminococcaceae, Dialister, Firmicutes, Clostridia, Clostridiales, Bifidobacteriales, and Faecalibacterium and negatively associated with Bacilli, Lactobacillales, Lachnospiraceae, and Porphyromonadaceae (P < 0.05). These results suggested that the relative abundance, diversity, and PICRUSt function predictions of male and female gut microbiomes differ significantly and that ADRB2 gene polymorphisms were associated with gut microbiome abundance in Chinese Han adolescents.
| S-EPMC10404897 | biostudies-literature
Project description:The role of the β2-adrenergic receptor (ADRB2) gene in patients with chronic obstructive pulmonary disease (COPD) is unclear. We investigated the association between ADRB2 variants and the risk of exacerbations in COPD patients treated with inhaled β2-agonists. Within the Rotterdam Study, a population-based cohort study, we followed 1,053 COPD patients until the first COPD exacerbation or end of follow-up and extracted rs1042713 (16Arg > Gly) and rs1042714 (27Gln > Glu) in ADRB2. Exposure to inhaled β2-agonists was categorised into current, past or non-use on the index date (date of COPD exacerbation for cases and on the same day of follow-up for controls). COPD exacerbations were defined as acute episodes of worsening symptoms requiring systemic corticosteroids and/or antibiotics (moderate exacerbations), or hospitalization (severe exacerbations). The associations between ADRB2 variants and COPD exacerbations were assessed using Cox proportional hazards models, adjusting for age, sex, use of inhaled corticosteroids, daily dose of β2-agonists, and smoking. In current users of β2-agonists, the risk of COPD exacerbation decreased by 30% (hazard ratio (HR); 0.70, 95% CI: 0.59-0.84) for each copy of the Arg allele of rs1042713 and by 20% (HR; 0.80, 95% CI: 0.69-0.94) for each copy of the Gln allele of rs1042714. Furthermore, current users carrying the Arg16/Gln27 haplotype had a significantly lower risk (HR; 0.70, 95% CI: 0.59-0.85) of COPD exacerbation compared to the Gly16/Glu27 haplotype. In conclusion, we observed that the Arg16/Gln27 haplotype in ADRB2 was associated with a reduced risk of COPD exacerbation in current users of inhaled β2-agonists.
| S-EPMC6912270 | biostudies-literature
Project description:BackgroundEffects of β(2)-adrenergic receptor gene (ADRB2) polymorphism on therapeutic responses to long-acting β(2)-adrenergic agonists have not been evaluated in long-term COPD trials. We aimed to investigate the effects of the ADRB2 Gly16Arg polymorphism on response to formoterol alone or in combination with the inhaled corticosteroid budesonide in patients with COPD.MethodsPatients ≥ 40 years of age with moderate to very severe COPD from the 12-month trial I (NCT00206167) or the 6-month trial II (NCT00206154) were randomly assigned to bid budesonide/formoterol pressurized metered-dose inhaler (pMDI) 320/9 μg or 160/9 μg, budesonide pMDI 320 μg + formoterol dry powder inhaler 9 μg (trial II), budesonide pMDI 320 μg (trial II), formoterol dry powder inhaler 9 μg, or placebo. The effect of Gly16Arg on predose FEV(1) and 1-h postdose FEV(1), exacerbations, diary variables, and adverse events were analyzed.ResultsNo significant interaction between genotype and treatment response was observed for predose (P ≥ .197) or postdose FEV(1) (P ≥ .125) in either pharmacogenetic study (n = 2,866). The number of COPD exacerbations per patient-treatment year was low and similar across genotypes for the active treatment groups (both studies). Percentages of patients with adverse events were similar across Gly16Arg genotype groups for each treatment.ConclusionTherapeutic response and tolerability to long-term treatment with formoterol alone or in combination with budesonide was not modified by ADRB2 Gly16Arg genotype in two large independent pharmacogenetic studies in patients with moderate to very severe COPD.
| S-EPMC3425335 | biostudies-literature
Project description:ObjectivesAsthma, the most frequent chronic respiratory disease, results from a complex interaction between multiple genes and environmental factors. To date, more than 100 candidate genes and single nucleotide polymorphisms (SNPs) have been reported to be associated with asthma. One of the discovered genes related to asthma is ADAM33. However, the relationship between ADAM33 gene polymorphisms and asthma is controversial. The aim of this study was to investigate the association between four ADAM33 gene SNPs and susceptibility to asthma in patients from southwestern Iran.Materials and methodsADAM33 gene polymorphisms at positions T+1 (rs2280091), T1 (rs3918396), S1 (rs2280089), and F+1 (rs511898) were examined in 150 patients with asthma and 149 age- and sex-matched healthy controls with a PCR-RFLP method.ResultsThere were no differences between patients and controls in allelic or genotype frequencies of ADAM33 SNPs. We found no associations between allelic or genotype distribution of the SNPs and spirometry indices, concomitant involvement of other allergic diseases, or exposure to cigarette smoke. In contrast to H4 haplotype, which appeared to be protective against asthma, inheritance of H2 and H3 haplotypes increased the risk of asthma up to 2-3 folds.ConclusionADAM33 gene polymorphisms appear to play a partial role in asthma susceptibility, investigation of expression changes in this gene in response to environmental factors or the local formation of a soluble form of the molecule in the lung can be helpful to elucidate the impact of this molecule in the induction of asthma.
| S-EPMC6118084 | biostudies-literature