Beta2-adrenergic Receptor Gene Polymorphisms Research Articles

Comparison of Beta-2 Adrenergic Receptor Gene Polymorphisms Between Patients with Fibromyalgia Syndrome and Healthy Controls.

Objectives This study aims to compare the beta-2 adrenergic receptor (ADRB2) gene polymorphisms of patients with fibromyalgia syndrome (FMS) with those of healthy control subjects, and to investigate the possible relationship between symptoms of FMS and polymorphisms of the ADRB2 gene.Patients and methods The study included 170 females (mean age 47.8±10.3 years; range, 21 to 75 years) diagnosed with FMS according to the 2010 American College of Rheumatology criteria and 170 healthy females (mean age 47.2±8.8 years; range, 20 to 72 years) as the control group. Several clinical symptoms of the participants related to FMS were questioned and recorded. The visual analog scale (VAS) and Fibromyalgia Impact Questionnaire (FIQ) scores of the fibromyalgia group were recorded. In both groups, the ADRB2 (rs1042717) single-nucleotide polymorphism was detected by way of a real-time polymerase chain reaction. The wild-type (Guanine/Guanine), the mutant type (Adenine/Adenine) and heterozygous type (Adenine/Guanine) were detected. The sample power was calculated considering the minor allele frequency.Results The comparison of the ADRB2 gene polymorphism between patients with FMS and the control subjects showed that the groups were similar in terms of ADBR2 gene polymorphism and genotype (p>0.05). There was no significant difference in terms of genotype when the ADRB2 gene polymorphisms in patients with FMS were compared in terms of clinical symptoms, VAS and FIQ scores (p>0.05).Conclusion Beta-2 adrenergic receptor (rs1042717) gene polymorphisms and genotype distribution are no different between patients with FMS and healthy individuals. ADRB2 gene polymorphisms in patients with FMS have no effect on clinical symptoms and VAS and FIQ scores. The results of the present study will light the way for future research into ADRB2 gene polymorphisms in the pathogenesis of FMS.

Beta-2 adrenergic receptor (ADRB2) gene polymorphism Arg16Gly as risk factor for osteoporosis

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Beta2-adrenergic receptor gene haplotypes and bronchodilator response in Egyptian patients with chronic obstructive pulmonary disease

PurposeChronic obstructive pulmonary disease (COPD) is a multi-factorial disorder caused by environmental determinants and genetic risk factors. Understanding the genetic predisposition of COPD is essential to develop personalized treatment regimens. Beta2-adrenergic receptor (ADRB2) gene polymorphisms have been implicated in the pathogenesis of obstructive pulmonary diseases. This study was conducted to assess the genetic association between Arg16Gly and Gln27Glu polymorphisms and COPD in the Egyptian patients, and to analyze their impact on the clinical outcome and therapeutic response. Patients/methodsThe study population included 115 participants (61 COPD patients and 54 healthy controls) were genotyped for the Arg16Gly (rs1042713) and Gln27Glu (rs1042714) polymorphisms. Pulmonary function test was done and repeated in patients after salbutamol inhalation. ResultsThe Gly16 and Gln27 alleles represented 57% and 70% of the whole study population, and only 3 haplotypes were detected; Arg16/Gln27, Gly16/Gln27, and Gly16/Glu27. Genotypes and haplotypes homozygous for Arg16 and Gln27 were more likely to develop COPD (p<0.05). However, individuals carrying Glu27 allele conferred protection against COPD development (p=0.002). Furthermore, Arg16 genotypes and haplotypes were significantly associated with higher grades of dyspnea, more COPD symptoms and frequent exacerbations. In contrast, patients carrying Glu27 allele had better bronchial airway responsiveness to β2-agonists. ConclusionsOur findings suggested that the ADRB2 gene polymorphisms may have vital role in COPD risk, severity, and bronchodilator response among Egyptian population. Larger epidemiological studies are needed for results validation.

P02. Beta-2 adrenergic receptor (ADRB2) gene polymorphisms as risk factors for reduced bone mineral density

P02. Beta-2 adrenergic receptor (ADRB2) gene polymorphisms as risk factors for reduced bone mineral density

(283) Beta2-adrenergic receptor gene polymorphisms and haplotypes associate with chronic pain in sickle cell disease

(283) Beta2-adrenergic receptor gene polymorphisms and haplotypes associate with chronic pain in sickle cell disease

ADRB2 Polymorphism and Salbutamol Responsiveness in Northern Indian Children with Mild to Moderate Exacerbation of Asthma.

The primary objective was to determine the association between beta-2 adrenergic receptor (ADRB2) gene polymorphism (rs1042713, c.46A>G, p.Arg16Gly) and the response to inhaled salbutamol in North Indian children aged 5 to 15 years, with mild to moderate exacerbation of asthma. This cross-sectional study was done at a tertiary-care hospital in Northern India from June 2011 to May 2013. 120 children with asthma with mild to moderate exacerbation underwent spirometry at baseline and after administration of three doses of salbutamol. An increase in FEV1 =15% was considered as positive response. Blood samples from these children were analysed for ADRB2 polymorphism (p.Arg16Gly). 94 non-asthmatic adult controls were also studied to determine the prevalence of ADRB2 polymorphism. In asthmatic children, the frequency of AA, GG, AG genotypes were 24.2%, 24.2% and 51.7% compared to 20.2%, 20.2% and 59.6%, respectively in the non-asthmatic adults. Salbutamol responsiveness showed no correlation with the studied ADRB2 polymorphism (p= 0.55). A trend towards greater bronchodilator responsiveness amongst AA genotype, compared to GG genotype was observed (Median change in percent predicted FEV1 14.5% and 7.5%, respectively). No correlation was found between salbutamol responsiveness and ADRB2 genotype in Northern Indian children with asthma with mild-to moderate exacerbation.

Are beta2-Adrenergic Receptor Gene Single-Nucleotide Polymorphisms Associated with Polycystic Ovary Syndrome? a Pharmacogenetic Study

Study background: Polycystic ovary syndrome (PCOS) is a common complex condition in women associated with reproductive, metabolic and psychological features. Evidences from studies on women with PCOS and on an experimental rat PCO model suggest that the sympathetic regulatory drive to the ovary may be unbalanced (hyperactivity). The aim of this study was to investigate polymorphism codon 16, 27,113 and 164 of beta2 adrenergic receptor in polycystic ovary syndrome (PCOS). Methods: 100 patients with PCOS from Infertility Center of Valie Asre, Imam Khomeini Hospital Complex participated in this study for the first time between May 2014-2015. All women aged 20-40 years and had a body mass index (BMI) were under 28. Results: Our results show that women with PCOS had polymorphism only in codon 164 with 44.4% (P< 0.002), that represents a significant difference between the study and control groups. Conclusion: Therefore Beta2 adrenergic receptor gene polymorphism (Thr164Ile) associates withpolycystic ovary syndrome. The ratio of heterozygotes to homozygotes shows a significant difference between the two groups.

A population-based case-control study to evaluate the role of codon 164 of beta 2-adrenergic receptor gene polymorphism in Iranian PCOS patients

A population-based case-control study to evaluate the role of codon 164 of beta 2-adrenergic receptor gene polymorphism in Iranian PCOS patients

Beta2-Adrenergic Receptor Gene Polymorphisms in Egyptian Patients with Acute Myocardial Infarction

Background. Beta2-adrenergic receptor (ADRB2) gene polymorphisms, Arg16Gly and Gln27Glu, have been implicated in the pathogenesis of cardiovascular diseases. The aim of this study was to determine the association of these two polymorphisms with the risk of myocardial infarction (MI) in the Egyptian population.Methods. Blood samples were collected from 68 MI patients and 75 healthy controls. They were assessed for the presence of cardiovascular risk factors and genotyped for the Arg16Gly (rs1042713) and Gln27Glu (rs1042714) polymorphisms using allelic-discrimination polymerase chain reaction.Results. There is no significant difference in genotype and allele frequencies at codon 16 between MI patients and controls (P=0.919). However, at codon 27, MI risk was higher in Gln27homozygous participants than in Glu27carriers (P=0.045). The haplotype frequency distribution showed significant difference among cases and controls (P=0.002); homozygotes for Gly16/Gln27haplotype were more susceptible to MI than Gly16/Glu27carriers. Patients with Arg16/Gln27haplotype had higher serum total cholesterol levels (P&lt;0.05) and lower frequency of diabetes in MI patients (P&lt;0.01). However, both Glu27genotypes and haplotype showed lower frequency of hypertension (P&lt;0.001).Conclusions. Our findings suggested that theADRB2gene polymorphisms may play an important role in susceptibility of MI among Egyptian population.

Beta-2 adrenergic receptor (ADRB2) gene polymorphisms and the risk of asthma: a meta-analysis of case-control studies.

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.

Association of Gln27Glu and Arg16Gly polymorphisms in Beta2-adrenergic receptor gene with obesity susceptibility: a meta-analysis.

BackgroundThe beta2-adrenergic receptor (ADRB2) gene polymorphism has been implicated in susceptibility to obesity, but study results are still controversial.ObjectiveThe present meta-analysis is performed to determine whether there are any associations between the Gln27Glu (rs1042714) or the Arg16Gly (rs1042713) polymorphisms in ADRB2 and obesity susceptibility.MethodsThe PubMed (1950–2014), Embase (1974–2014), and China National Knowledge Infrastructure (CNKI, 1994–2014) databases were searched using the search terms (“Beta2-adrenergic receptor”, “β2-adrenergic receptor” or “ADRB2”), “polymorphism,” and “obesity”. Fixed- or random-effects pooled measures were determined on the bias of heterogeneity tests across studies. Publication bias was examined by Egger's test and the modified Begg's test.ResultsEighteen published articles were selected for meta-analysis. Overall analyses showed that rs1042714 (Gln27Glu) was associated with significantly increased obesity risk in the heterozygote model (Gln/Glu vs. Gln/Gln: OR: 1.16, 95% CI: 1.04–1.30, I 2 = 49%, P = 0.009) and the dominant model (Gln/Glu + Glu/Glu vs. Gln/Gln: OR: 1.2, 95% CI: 1.00–1.44, I 2 = 55%, P = 0.04), whereas no significant association was found in the other models for rs1042714. Also, no significant association was found between the rs1042713 (Arg16Gly) gene polymorphism and the risk of obesity in all genetic models. In addition, neither rs1042713 (Arg16Gly) nor rs1042714 (Gln27Glu) showed any significant association with obesity susceptibility when the population were stratified based on gender.ConclusionOur meta-analysis revealed that the rs1042714 (Gln27Glu) polymorphism is associated with obesity susceptibility. However, our results do not support an association between rs1042713 (Arg16Gly) polymorphisms and obesity in the populations investigated. This conclusion warrants confirmation by more case-control and cohort studies.

Roles of beta2-adrenergic receptor gene polymorphisms in a Turkish population with obstructive sleep apnea syndrome or obesity.

We determined the distribution of the Arg16Gly and Gln27Glu polymorphisms of the beta-2 adrenergic receptor gene (ADRB2) in patients with obstructive sleep apnea syndrome as well as a control group in Northeastern Turkey. A total of 52 patients diagnosed with obstructive sleep apnea in a sleep laboratory and 78 control subjects were examined. Peripheral blood samples were taken from patients diagnosed with obstructive sleep apnea by polysomnography. DNA was extracted from blood samples and amplified using polymerase chain reaction. Amplification products were digested with restriction enzymes to investigate gene polymorphisms. Restriction products were extracted from agarose gel electrophoresis and polymorphisms were analyzed using gel images. The Arg16Gly polymorphism was observed in 18 of 52 patients and in 23 of 78 controls. The Gln27Glu polymorphism was observed in 21 of 52 patients and in 28 of 78 controls. In conclusion, there was no correlation among polymorphic frequencies between patient and control groups. Based on the results, these polymorphisms do not contribute to the clinical diagnosis of this syndrome. However, the distribution of Arg16Gly vs Gln27Glu polymorphisms may contribute to obesity in patients with a body mass index greater than 30 (P < 0.05). Different results may be obtained if the parameters of obstructive sleep apnea disease are changed.

Association of beta 2 -adrenergic receptor gene polymorphisms and nocturnal asthma in Saudi patients

BACKGROUND AND OBJECTIVES:Two polymorphisms of beta2-adrenergic receptor (β2-AR) gene, namely the substitution from arginine (Arg) to glycine (Gly) at codon 16 and from glutamine (Gln) to glutamic (Glu) at codon 27, are linked with functional changes in the β2-AR in the respiratory system even though they are not deemed to be susceptibility genes for asthma per se. The objective of this study was to investigate this association in a subset of asthmatic patients, namely those with nocturnal asthma.METHODS:The β2-AR gene polymorphisms at codon 16 and 27 were assessed in 40 patients clinically diagnosed with nocturnal asthma and 96 normal controls. Genomic DNA was obtained from whole blood and genotyping was carried out by a PCR based restriction fragment length polymorphism technique.RESULTS:There was a statistically significant difference in genotype frequencies at codon 16 (Arg/Gly) between nocturnal asthmatic patients and normal control subjects (P < 0.05). However, there was no statistically significant difference in allele frequencies between the two groups. In addition, there was a significant association between Arg16-Gly genotype with nocturnal asthma compared to homozygous Gly16 (codominant model P = 0.0033, OR = 3.69: 95% CI: 1.49-9.12). However, there were no statistically significant differences in genotype and allele frequencies at codon 27 (Gln/Glu) between the normal control and nocturnal asthmatic groups (χ2 = 1.81, P = 0.41). The results also indicate that linkage disequilibrium existed between the β2-AR codon 16 and β2-AR codon 27 polymorphism (|D´| = 0.577). The data for all haplotypes did not show a statistically significant association.CONCLUSION:We present the genotype and allele frequencies of β2-AR gene polymorphisms in normal Saudi subjects and nocturnal asthmatic patients. There was a significant difference in genotype frequencies at codon 16 (Arg/Gly). However, our study indicates a poor association of individual single nuceotide polymorphisms with nocturnal asthma.

Beta2-adrenergic receptor gene polymorphisms as systemic determinants of healthy aging in an evolutionary context

The Gln 27Glu polymorphism but not the Arg 16Gly polymorphism of the beta2-adrenergic receptor (ADRB2) gene appears to be associated with a broad range of aging-associated phenotypes, including cancers at different sites, myocardial infarction (MI), intermittent claudication (IC), and overall/healthy longevity in the Framingham Heart Study Offspring cohort. The Gln 27Gln genotype increases risks of cancer, MI and IC, whereas the Glu 27 allele or, equivalently, the Gly 16Glu 27 haplotype tends to be protective against these diseases. Genetic associations with longevity are of opposite nature at young-old and oldest-old ages highlighting the phenomenon of antagonistic pleiotropy. The mechanism of antagonistic pleiotropy is associated with an evolutionary-driven advantage of carriers of a derived Gln 27 allele at younger ages and their survival disadvantage at older ages as a result of increased risks of cancer, MI and IC. The ADRB2 gene can play an important systemic role in healthy aging in evolutionary context that warrants exploration in other populations.

Probable Role of Beta 2-Adrenergic Receptor Gene Haplotype in Toluene Diisocyanate-Induced Asthma

PurposeA genetic polymorphism of the beta 2-adrenergic receptor is a major factor associated with the asthmatic phenotype. The association of this polymorphism with toluene diisocyanate (TDI)-induced asthma has not been investigated. We examined 103 TDI-induced asthma patients (TDI-OA), 60 asymptomatic exposed controls (AEC), and 263 unexposed healthy controls (NC) in order to identify beta 2-adrenergic receptor gene (ADRB2) polymorphisms and the possible association with TDI-induced asthma.MethodsSingle nucleotide polymorphisms (SNPs) of ADRB2 were genotyped by direct sequencing. Serum-specific IgE and IgG levels were measured using an enzyme-linked immunosorbent assay. Phenotypes and clinical patient parameters were compared.ResultsSNPs were identified (-47 T>C, -20 T>C, Arg16Gly A>G, Gln27Glu C>G, Leu134Leu G>A, Arg175Arg C>A) during ADRB2 screening (from -231 to 793 bp). No significant differences in allelic and genotypic frequencies were noted for any of the six ADRB2 SNPs. The Arg16Gly A>G, Leu134Leu G>A, and Arg175Arg C>A SNPs and haplotype 1 [TTACGC] were significantly associated with specific IgE antibodies to the TDI-human serum albumin (HSA) conjugate in TDI-exposed subjects (P<0.05). Exposed workers with the ADRB2 ht1/ht1 homozygote had a significantly higher TDI-HSA conjugate-specific IgE sensitization rate than did those with the null ht1 haplotype (odds ratio, 15.40; 95% confidence interval, 1.81-131.06).ConclusionsADRB2 polymorphisms may affect IgE-specific sensitization to TDI-HSA conjugate in TDI-exposed workers.

Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly in patients with heart failure

Background -Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly and Thr164Ile were suggested to have an effect in heart failure. We evaluated these polymorphisms relative to clinical characteristics and prognosis of alarge cohort of patients with heart failure of different etiologies.Methods -We studied 501 patients with heart failure of different etiologies. Mean age was 58 years (standard deviation 14.4 years), 298 (60%) were men. Polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism.Results -During the mean follow-up of 12.6 months (standard deviation 10.3 months), 188 (38%) patients died. Distribution of genotypes of polymorphism Arg16Gly was different relative to body mass index (χ2 = 9.797;p = 0.04). Overall the probability of survival was not significantly predicted by genotypes of Gln27Glu, Arg16Gly, or Thr164Ile. Allele and haplotype analysis also did not disclose any significant difference regarding mortality. Exploratory analysis through classification trees pointed towards a potential association between the Gln27Glu polymorphism and mortality in older individuals.Conclusion -In this study sample, we were not able to demonstrate an overall influence of polymorphisms Gln27Glu and Arg16Gly of beta-2 receptor gene on prognosis. Nevertheless, Gln27Glu polymorphism may have a potential predictive value in older individuals.

The effects of beta2 adrenergic receptor gene polymorphism in lipid profiles

BackgroundExplore the interaction between apolipoprotein E (Apo E), phospholipase A2 (PLA2) and β2 adrenergic receptor (β2-AR) gene polymorphisms and lipid profiles in an elderly Chinese population.MethodsFive hundred subjects aged 65 to 74 years were randomly selected from a community in southern Taiwan to assess the relationship between Apo E, PLA2 and β2-AR gene polymorphisms and lipid profiles. Two hundred sixty-seven participants agreed to have venous blood drawn for DNA studies.ResultsTwo statistically significant differences were noted in TC and LDL-C in the Gln27Glu of the β2-AR gene polymorphism (P = 0.007, P = 0.022). The low-income group had a higher HDL-C level (p = 0.076). The Gln27Glu polymorphism Glu/Glu or Gln/Glu subjects had lower TC levels compared to the Gln27Glu polymorphism Gln/Gln subjects (p = 0.092). Lower TC levels (p = 0.082) and lower LDL-C levels (p = 0.045) in subjects with the Cys19Arg16Glu27 haplotype. Lower TC levels (p = 0.06) were also noted in subjects with the Cys19Gly 16Glu27 haplotype. On the other hand, higher VLDL-C levels (p = 0.185) and higher triglyceride (TG) levels (p = 0.190) were noted in subjects with the Cys19Gly 16Gln27 haplotype. The ε2 allele combined with low income had a positive effect on HDL-C (p = 0.0011), after adding the income factor in this study.ConclusionWhen the effects of Apo E and PLA2 on lipid profiles were included in this study, β2-AR gene polymorphisms reduced significant effect on lipid profiles. Similarly, low income increased effect on HDL-C. This study appeared that the results of gene-gene and gene-environment interaction, it should be considered in further studies for lipid profiles.

An improved rapid genotyping method for the study of beta-2 adrenergic receptor gene polymorphisms using single tube allele specific multiplex PCR

Seventeen single nucleotide polymorphisms (SNPs) have been identified so far, within the beta-2 receptor (beta(2) AR) gene. The presence of so many SNPs within the beta(2) AR gene causes a problem, for those studying beta(2) AR pharmacogenetics, in relation to which SNPs to choose. Most of the work has focused on the three common SNPs within the coding block (alleles 16, 27 and 164) and the techniques developed have been for these three functionally important alleles. We report an improved polymerase chain reaction (PCR)-based method for the simultaneous detection of five functionally important beta(2) AR alleles, namely beta 16A/G, beta utr-20C/T, beta 27C/G, beta utr-47C/T and beta 164C/T. Genomic DNA was used as a template for duplex and triplex PCR to detect the polymorphic sites of the five alleles. DNA sequencing analysis confirmed the specificity of this PCR method. This simplified single-tube multiplexed PCR assay provides an easier, faster and more cost-effective method than those available for studying the specified polymorphisms of the beta(2)AR gene.

Beta 2-adrenergic receptor polymorphisms: pharmacogenetic response to bronchodilator among African American asthmatics.

Beta2-adrenergic receptor (beta2AR) gene polymorphisms have been reported to be associated with various asthma-related traits in different racial/ethnic populations. However, it is unknown whether beta2AR genetic variants are associated with asthma in African Americans. In this study, we have examined whether there is association between beta2AR genetic variants and asthma in African Americans. We have recruited 264 African American asthmatic subjects and 176 matched healthy controls participating in the Study of African Americans, Asthma, Genes and Environments (SAGE). We genotyped seven known and recently identified beta2AR SNP variants, then tested genotype and haplotype association of asthma-related traits with the beta2AR SNPs in our African American cohort with adjustment of confounding effect due to admixture background and environmental risk factors. We found a significant association of the SNP -47 (Arg-19Cys) polymorphism with DeltaFEF(25-75), a measure of bronchodilator drug responsiveness, in African American asthmatics after correction for multiple testing (P = 0.001). We did not observe association of the SNP +46 (Arg16Gly) variant with asthma disease diagnosis and asthma-related phenotypes. In contrast to previous results between the Arg16Gly variant and traits related to bronchodilator responsiveness, our results indicate that the Arg-19Cys polymorphism in beta upstream peptide may play an important role in bronchodilator drug responsiveness in African American subjects. Our findings highlight the importance of investigating genetic risk factors for asthma in different populations.

Mo-P6:450 Beta2-adrenergic receptor gene polymorphisms do not predict cardiovascular disease in the general

Mo-P6:450 Beta2-adrenergic receptor gene polymorphisms do not predict cardiovascular disease in the general