ADRB2 Polymorphisms Research Articles

Influence of ADRB1, ADRB2, and COMT Genetic Polymorphisms on Postoperative Outcomes of Patients Undergoing Cardiac Valve Surgery

PurposeThe aim of this study is to prospectively investigate the influence of ADRB and COMT gene polymorphisms on postoperative outcomes of patients undergoing cardiac surgery. MethodsThis prospective cohort study included 223 patients undergoing elective cardiac valve surgery using cardiopulmonary bypass. Demographic information, intraoperative data, postoperative data, and blood samples were collected. Patients were genotyped for single-nucleotide polymorphisms (SNPs) of ADRB1 rs1801253, ADRB2 rs1042713, and COMT rs4680. Major adverse cardiovascular and cerebrovascular events (MACCEs) were used as the primary outcome to evaluate the postoperative prognosis of patients. Secondary outcomes included the duration of mechanical ventilatory support, intensive care unit stay, postoperative hospital stay, and postoperative need of inotropic or vasoactive agents. FindingsThe overall incidence of MACCEs was 15.2%. Among 3 SNP loci, only different genotyped carriers of ADRB2 rs1042713 had statistically significant differences in the incidence of MACCEs (P = 0.005), especially for acute kidney injury (P = 0.023). The proportions of postoperative norepinephrine demand of patients carrying the AA genotype of ADRB2 rs1042713 (P = 0.016) and the AG genotype of COMT rs4680 (P = 0.018) were low. The duration of mechanical ventilatory support (P = 0.034) and postoperative hospital stay (P = 0.045) of patients carrying the AG genotype of COMT rs4680 was shortest. After multiple logistic regression analysis, we found that the G allele carriers of ADRB2 rs1042713 had a higher risk of MACCEs (AG vs AA genotype: odds ratio [OR] = 4.348; 95% CI, 1.529–12.359, P = 0.006; GG vs AA genotype: OR = 3.722; 95% CI, 1.060–13.071; P = 0.040), in particular with acute kidney injury (AG vs AA genotype: OR = 5.273; 95% CI, 1.093–25.451; P = 0.038; GG vs AA genotype: OR = 7.533; 95% CI, 1.275–44.522; P = 0.026). There was no SNP-SNP interaction found among the 3 SNPs with multifactor dimensionality reduction analysis. ImplicationThe ADRB2 rs1042713 polymorphism might be related to prognosis of patients undergoing cardiac surgery. Patients carrying the G allele of ADRB2 rs1042713 had a higher risk of developing MACCEs, especially acute kidney injury. chictr.org.com identifier: ChiCTR1800015105.

Influence of b2 adrenergic receptor polymorphism (rs1042713 and rs1042714) on anthropometric, hormonal and lipid profiles in polycystic ovarian syndrome.

BackgroundPolycystic ovarian syndrome (PCOS) is a frequently encountered disorder. This study aimed to identify polymorphisms in ADRB2 in Saudi PCOS development and to study its influence on lipids, hormones, and anthropometric parameters.MethodsSaudi females (100) suffering from PCOS and healthy controls (100) were investigated. The estimation of cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), plasma glucose, leptin Insulin, and ghrelin were carried out. The DNA was extracted, and ADRB2 fragment carrying the exon 1 was amplified and sequenced.ResultsThe waist, W/H ratio, lipids, glucose, and insulin were significantly higher in the obese PCOS compared to the normal weight group. The leptin and ghrelin were not different. Two single nucleotide polymorphisms (SNPs): rs1042713 (Arg16Gly; A>G) and rs1042714 (Gln27Glu; C>G) were identified. The genotype and allele frequency of rs1042713 did not differ in the total PCOS and normal weight, and obese PCOS compare to the controls. However, rs1042714 was significantly associated with PCOS development, where the minor G allele was protective against PCOS development.ConclusionsThe rs1042714 polymorphism of the ADRB associates with PCOS development in Saudis, while rs1042713 does not. However, the GG genotype of rs1042713 associates significantly with elevated BMI, waist, hip, W/H, and leptin, and decreased ghrelin. On the other hand, rs1042714 genotypes do not associate with any abnormality except the homozygous GG have higher triglycerides and lower HDL-C. Interestingly, glucose showed different correlation patterns in individuals carrying different genotypes of the two studied SNP, indicating clearly that the metabolic responses to a normal nutrient are significantly influenced by the genotypes of the SNPs in ADRB2.

Роль полиморфизма β2-адренорецепторов в развитии сердечно-сосудистых осложнений при пневмонииях тяжелого течения при гриппе АH1N1/09 в 2019 году в Забайкальском крае

The purpose of the study. Th e aim of this study was to study the polymorphism of the ADRB2 gene, as well as the frequency and nature of cardiovascular complications in its presence in patients with severe pneumonia with infl uenza A/H1N1/09. Material and methods. Th e study included 100 patients with pneumonia with infl uenza A/H1N1 / 09 in 2019 in the Trans-Baikal Territory. All patients were treated in the intensive care unit. In patients, the causative agent-infl uenza virus A/H1N1 / 09 was verifi ed by PCR-detection of the pathogen in nasopharyngeal smears or hemagglutination inhibition test (HIT) with an increase in the antibody titer in paired sera. DNA was isolated from peripheral blood leukocytes; fragments were amplifi ed by polymerase reaction and genotyped by short fragment length polymorphism for Gln27Glu and Arg16Gly ADRB2. Results. The patients were divided into 2 groups: Group I (n=41) – patients with cardiovascular complications; group II (n=59) – patients without cardiovascular complications. Th e groups were comparable in gender and age. Among the cardiovascular complications prevailed: arrhythmias (n=13); decompensation of chronic heart failure (n=13); acute myocardial infarction (n=7); pulmonary embolism (n=5); myocarditis/pericarditis (n=3). When studying the ADRB2 polymorphism, it was found that the most unfavorable variant is the homozygous mutation Arg16Gly (Gly/Gly). This mutation was detected in 6 (14.6 %) patients in group I, but was not detected in group II (P=0.003). In the presence of this mutation in patients with severe secondary viral-bacterial pneumonia with infl uenza A/H1N1 / 09, the risk of developing cardiovascular complications increases (HR=2.6; CI 2.06; 3.49). Conclusion. Patients with severe pneumonia during the A/H1N1/09 infl uenza epidemic in 2019 had a high incidence of cardiovascular complications (41 %). The presence of the homozygous Arg16Gly mutation (Gly/Gly) increases the risk of cardiovascular complications by 2.06 times, and the presence of the heterozygous Arg16Gly mutation (Arg/Gly) reduces this risk by 0.5 times

Modulation of IL-17A and IFNγ by β2-adrenergic agonist terbutaline and inverse-agonist nebivolol, influence of ADRB2 polymorphisms

<abstract><sec> <title>Background</title> <p>Upon activation, helper T (Th) cells produce cytokines such as IL-17A and IFNγ, which may exacerbate inflammatory disease and disorders. Adrenergic drugs are emerging as immunomodulatory agents to treat pro-inflammatory diseases, but their function is not completely understood. Th Cells express the β2-adrenergic receptor (β2AR) that is encoded by <italic>ADRB2</italic>. Agonists of the β2AR decrease IFNγ but can increase IL-17A from Th cells. We compared a β2AR agonist to an inverse-agonist, and assessed the influence of <italic>ADRB2</italic> polymorphisms on IL-17A and IFNγ responses.</p> </sec><sec> <title>Methods</title> <p>Peripheral blood mononuclear cells (PBMCs) from venous blood of healthy human participants were cultured with T cell activators anti-CD3 and anti-CD28 antibodies. Terbutaline, a β2AR agonist or nebivolol, a β1AR antagonist and β2AR inverse-agonist, were added <italic>in vitro</italic>. Cytokines IL-17A and IFNγ were measured using enzyme-linked immunosorbent assay. Genomic <italic>ADRB2</italic> and its immediate upstream region were sequenced using Sanger's method. Cytokine response to drug was analyzed based on <italic>ADRB2</italic> polymorphisms.</p> </sec><sec> <title>Results</title> <p>Terbutaline consistently inhibited IFNγ from activated PBMC samples. In contrast, it increased IL-17A in PBMC homozygous for Gly16 codon of <italic>ADRB2</italic>. Nebivolol inhibited IL-17A and IFNγ from activated Th cells. When applied to activated-PBMCs, nebivolol inhibited IL-17A but did not significantly inhibit IFNγ although a trend was observed. The ability of nebivolol to inhibit IL-17A was attenuated by a β2AR-specific antagonist. Cellular proliferation and viability was not significantly changed by nebivolol. Nebivolol suppressed IL-17A in all of the samples regardless of <italic>ADRB2</italic> polymorphisms.</p> </sec><sec> <title>Conclusions</title> <p>This data demonstrates that terbutaline inhibited IFNγ, however, it increased IL-17A in samples with the common Gly16 polymorphism of <italic>ADRB2</italic>. Nebivolol inhibited IL-17A regardless of <italic>ADRB2</italic> polymorphisms. Thus, nebivolol is a strong candidate for treating inflammatory diseases or disorders where IL-17A exacerbates symptoms.</p> </sec></abstract>

Beta-3-adrenergic Receptor rs4994 Polymorphism Is a Potential Biomarker for the Development of Nonalcoholic Fatty Liver Disease in Overweight/Obese Individuals.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases. Obesity is the most common and well-established risk factor for NAFLD, but there are large interindividual differences in the relationship between weight status and the development of NAFLD. Beta-3-adrenergic receptor (ADRB3) plays a key role in the development of visceral obesity and insulin resistance; however, the effect of ADRB3 polymorphisms on the risk of NAFLD remains unclear. We investigated whether or not a common rs4994 polymorphism (T190C) in the ADRB3 gene is associated with the risk of NAFLD through an increase in the body mass index (BMI) among the general population. We performed cross-sectional and longitudinal analyses in a total of 591 Japanese health screening program participants. Among the overweight or obese subjects, but not normal-weight subjects, individuals with the C/C genotype had a higher risk of developing NAFLD in comparison to those with other genotypes in the cross-sectional analysis (odds ratio: 4.40, 95% confidence interval (CI): 1.08–17.93). Meanwhile, the receiver operating characteristic curve indicated that the association between an increase in the BMI and the presence of NAFLD in subjects with the C/C genotype (area under the curve: 0.91, 95% CI: 0.78–1.00) was more pronounced in comparison to subjects with other genotypes. These above-described findings were verified by the analyses using a replicated data set consisting of 5,000 random samples from original data sets. Furthermore, among the 291 subjects for whom longitudinal medical information could be collected and who did not have NAFLD at baseline, the Cox proportional hazard model also confirmed that overweight or obese status and the C/C genotype were concertedly related to the increased risk of NAFLD development. These results suggest that genotyping the ADRB3 rs4994 polymorphism may provide useful information supporting the development of personalized BMI-based preventive measures against NAFLD.

Relation of ADRB3, GEF, ROCK2 gene polymorphisms to clinical findings in overactive bladder.

Adrenergic and cholinergic pathways play an important role in contraction-relaxation harmony in human bladder. Functional changes in any proteins in these pathways may result in overactive bladder. We aimed to investigate whether single gene polymorphisms affecting adrenergic and cholinergic pathways are associated with OAB syndrome. 60 patients with idiopathic OAB and 60 healthy controls were included in the study. A validated OAB-V8 questionnaire was given to all patients. Polymorphisms of ADRB3, ROCK2, and GEF gene were detected by PCR from whole blood samples. Genotypic structures of patients and controls were compared. The relationship between genotypic structures and OAB symptom scores were investigated. We found no significant difference in the genotype and allele frequencies between the patients and controls for all three SNP. While there was no relationship between ADRB3 and GEF gene polymorphisms and OAB scores in OAB patients, the OAB score in heterozygous polymorphic individuals was significantly higher than in homozygous polymorphic individuals in the ROCK2 gene (p = 0.039). The polymorphisms of the ADRB3, ROCK2, and GEF genes were present in both OAB group and healthy controls, but were not associated with OAB syndrome.

Genetic variability of five ADRB2 polymorphisms among Mexican Amerindian ethnicities and the Mestizo population.

The Mexican population is characterized by high and particular admixture, and the picture of variants associated with disease remains unclear. Here we investigated the distribution of single nucleotide polymorphisms (SNPs) in the Mexican population. We focused on two non-synonymous and three synonymous SNPs in the beta-2 adrenergic receptor gene (ADRB2), which plays key roles in energy balance regulation. These SNPs were genotyped in 2,011 Mexican Amerindians (MAs) belonging to 62 ethnic groups and in 1,980 geographically matched Mexican Mestizos (MEZs). The frequency distribution of all five ADRB2 variants significantly differed between MAs, MEZs, and other continental populations (CPs) from the 1000 Genomes database. Allele frequencies of the three synonymous SNPs rs1042717A, rs1042718A, and rs1042719C were significantly higher in Mexican individuals, particularly among MAs, compared to in the other analyzed populations (P<0.05). The non-synonymous ADRB2 Glu27 allele (rs1042714G), which is associated with several common conditions, showed the lowest frequency in MAs (0.03) compared to other populations worldwide. Among MEZs, this allele showed a frequency of 0.15, intermediate between that in MAs and in Iberians (0.43). Moreover, Glu27 was the only SNP exhibiting a geographic gradient within the MEZ population (from 0.22 to 0.11), reflecting admixed mestizo ancestry across the country. Population differentiation analysis demonstrated that Glu27 had the highest FST value in MAs compared with Europeans (CEU) (0.71), and the lowest between MAs and Japanese (JPT) (0.01), even lower than that observed between MAs and MEZs (0.08). This analysis demonstrated the genetic diversity among Amerindian ethnicities, with the most extreme FST value (0.34) found between the Nahuatls from Morelos and the Seris. This is the first study of ADRB2 genetic variants among MA ethnicities. Our findings add to our understanding of the genetic contribution to variability in disease susceptibility in admixed populations.

Association between ADRB2, IL33, and IL2RB gene polymorphisms and lung cancer risk in a Chinese Han population

PurposeThis study aimed to explore the associations between polymorphisms of a very important pharmacogene, ADRB2, two inflammation-related genes, IL33 and IL2RB, and the risk of lung cancer. MethodsSix polymorphisms of ADRB2, IL33, and IL2RB were genotyped in 300 lung cancer patients and 300 healthy controls using MassARRAY. The relationship between genotypes and lung cancer risk was evaluated using chi-square tests. ResultsThe minor allele of rs1042711 was a risk allele for lung cancer, whereas the minor alleles of rs7025417 and rs5756523 had protective effects against lung cancer (p＜0.05). The CT genotype of rs1042711 and the GT genotype of rs1560642 were associated with increased risk of lung cancer, whereas the CC and AA genotypes of rs7025417 and the CT and CC genotypes of rs5756523 were associated with decreased disease risk (p < 0.05). Genetic model analysis shows that rs1042711 and rs1560642 were associated with increased risk of lung cancer; whereas rs7025417, rs5756523, and rs2284033 were associated with decreased disease risk (p < 0.05). Stratification analysis showed that rs1042711 and rs1560642 were associated with increased risk of lung cancer in nonsmokers and smokers, respectively, whereas rs7025417 and rs5756523 were associated with decreased disease risk in both subgroups (p＜0.05). ConclusionOur results shed new light on the association between polymorphisms of ADRB2, IL33, and IL2RB and the risk of lung cancer.

Polymorphisms in COMT, ADRB2 and HTR1A genes are associated with temporomandibular disorders in individuals with other arthralgias

ABSTRACT Objective: To evaluate the association between polymorphisms in genes and comorbid presence of arthralgias and TMD. Methods: This is a case-control study. The groups formed were individuals with chronic arthralgia and 1) myofascial pain (n = 42); 2) articular (n = 16); 3) multiple diagnoses (n = 69); 4) with TMD and without some other arthralgia (n = 16); 5) without TMD but with pain in other joints (n = 82); and 6) a control group (n = 72). SNPs in COMT, ADRB2, and HTR1A genes were investigated. Results: The CT genotype for the COMT (rs9332377) gene was associated with the absence of myofascial pain (p = .05). In the ADRB2 (rs1042713) gene, the AA genotype was associated with the absence of myofascial pain (p = .03). Discussion: This study supports the hypothesis that alterations in the COMT, ADRB2, and HTR1A genes influence the presence of chronic pain and TMD.

Genotyping Method and Frequency of ADRB3-rs4994 Single Nucleotide Polymorphism Genotypes in Hanoi 3-5 Years Old Chidren

Genotyping Method and Frequency of ADRB3-rs4994 Single Nucleotide Polymorphism Genotypes in Hanoi 3-5 Years Old Chidren

Correlation study on β2-adrenergic receptor gene polymorphisms and asthma susceptibility: evidence based on 57 case-control studies.

Previous studies have indicated that β2-adrenergic receptor (ADRB2) genetic polymorphism is related to the risk of asthma, but the results still have some controversy and uncertainty. To this end, the meta-analysis was performed, including all studies that can be used to assess the correlation between ADRB2 polymorphism and asthma susceptibility. The related papers on ADRB2 polymorphisms and asthma were systematically reviewed in databases of PubMed, EMBASE, Cochrane Library, and WanFang, Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were measured. The sensitivity analysis and publication bias were evaluated to investigate the correlation. This meta-analysis included 57 papers in total involving 11,157 cases and 12,281 controls. Results illustrated that the C79G variant genotypes owned a reduced effect on asthma susceptibility (G vs. C: OR=0.94, p=0.037). In the age stratification analysis, C79G polymorphism owned a reduced effect on asthma risk for children (GG vs. CC: OR=0.69, p=0.002; GG vs. CC+CG: OR=0.65, p<0.001). Furthermore, in the ethnic stratification analysis, the C79G variant genotypes also owned a reduced effect on asthma in Asians (GG vs. CC: OR=0.80, p=0.027; GG vs. CC+CG: OR=0.81, p=0.02). Besides, for A46G polymorphism, the ethnic stratification analysis demonstrated that the A46G variant owned an increased effect on asthma susceptibility among Caucasians (G vs. A: OR=1.15, p=0.043). For C491T polymorphism, a considerable reduced effect was found between C491T and asthma susceptibility for children (CT vs. CC: OR=0.70, p=0.03). In the ethnic stratification analysis, the effect was also considerable in the Caucasian subjects. The present meta-analysis demonstrated that C79G and C491T polymorphism may be a defensive factor for asthma, while A46G polymorphism may be a risk factor for asthma among the Caucasian population.

Impact of Beta adrenergic receptors polymorphism on the onset of ventricular fibrillation during the acute phase of myocardial infarction

Ventricular fibrillation complicating acute myocardial ischemia is the main cause of sudden cardiac death. We investigated whether two known ADBR2 and ADRB1 polymorphisms are associated with ventricular fibrillation (VF) in the context of myocardial infarction (MI). A total of 831 patients were recruited during the MAP-IDM study: 392 patients who experienced VF during the acute phase of primary MI and 439 controls with MI without VF. Patients were genotyped for the ADRB2 Gln27Glu, the ADRB1 Arg389Gly polymorphisms by RT-PCR. Unconditional logistic regression models were fitted, after adjustment on center, age and sex. Age was included as a 5 age-group variable (27–44, 45–54, 55–64, 65–74, 75–88) using dummy variables, including interaction terms between sex and age-groups. Cases and controls did not differ significantly in age, in sex-ratio, BMI, in smoker ratio and in troponin peak value. VF patients have a lower left ventricular ejection fraction (LVEF) (46.1% vs. 51.9%, P < 0.001). We observe a protective effect of polymorphism homozygous ADRB1-Gly49Gly (OR = 0.15, P = 0.03) and a slight tendency to risk sudden death for ADRB1-Arg389Arg (non significative). Analysis revealed a risk effect for polymorphism heterozygous ADRB2 Gln27Glu regarding a faster delay in the occurrence of FV ( P < 0,05). The ADRB2 Gln27Glu variant seems to predispose patients to fast onset VF in the setting of cardiac ischemia whereas the homozygous ADRB1Gly49Gly variant seems to protect patient to VF in the context of myocardial infarction.

Beta2-Adrenergic Receptor Polymorphisms and Haplotypes Associate With Chronic Pain in Sickle Cell Disease.

Pain in sickle cell disease (SCD) is severe, variable, and inadequately comprehended. The β2-adrenergic receptor (ADRB2) is critical in mediating neurotransmitter response in the sympathetic nervous system. In this association study, we examined 16 single nucleotide polymorphisms (SNPs) covering 5′-UTR and coding regions of ADRB2 for pain variability in SCD. Subjects recorded their non-crisis, baseline pain experience on a computerized tool from which we obtained chronic pain measurement score- composite pain index (CPI). Regression models yielded significant associations between chronic pain and seven SNPs. Non-synonymous SNP rs1042713 A allele (Arg16) caused a 5.73-fold decrease in CPI (p = 0.002). Allele A of rs12654778 and T of rs17778257 reduced CPI by a fold of 4.52 (p = 0.019), and 4.39 (p = 0.032), respectively. Whereas, in the 5′ UTR, allele C of rs1042711, G of rs11168070, C of rs11959427, and C of rs1801704 increased CPI by a fold of 10.86 (p = 0.00049), 5.99 (p = 0.016), 5.69 (p = 0.023), and 5.26 (p = 0.031), respectively. Together, these SNPs accounted for 2–15% of CPI variance after adjusting for covariates. Moreover, these SNPs were in high linkage disequilibrium (LD) showing three LD blocks in our cohort. A 10-marker haplotype increased CPI by 11.5-fold (p = 0.000407). Thus, ADRB2 polymorphisms might contribute to chronic pain severity and heterogeneity in SCD.

β2-Adrenergic Receptor Gene Polymorphisms Are Associated with Cardiovascular Events But not All-Cause Mortality in Coronary Artery Disease Patients: A Meta-Analysis of Prospective Studies.

Aims: β-Adrenergic receptors (ADRBs) play a pivotal role in cardiovascular disease. Recently, genetic polymorphisms of ADRB1 and ADRB2 have been suggested to be associated with cardiovascular events and all-cause mortality in coronary artery disease (CAD) patients, but the results of relevant studies are inconsistent and controversial. Therefore, we performed a meta-analysis to investigate the association between ADRB1 and ADRB2 polymorphisms with cardiovascular events and all-cause mortality in CAD patients.Materials and Methods: The PubMed, Ovid, EMBASE, Cochrane, and CINAHL databases were searched for eligible studies published before April 2018. A total of 5495 patients from eight studies were included in our meta-analysis.Results: We found that CAD patients harboring the ADRB2 rs1042714 Glu27 allele exhibited a positive association with cardiovascular events (risk ratio [RR] = 1.31, 95% confidence interval [CI]: 1.08–1.58, p = 0.006), but not with all-cause mortality (RR = 0.97, 95% CI: 0.70–1.35, p = 0.859), compared with patients who were Gln27 homozygotes. No other significant associations were observed between ADRB1 (rs1801252, rs1801253), ADRB2 (rs1042713, rs1800888) polymorphisms and cardiovascular events or all-cause mortality in CAD patients.Conclusion: This study suggests that the identified ADRB2 polymorphism could influence the outcomes of CAD patients, showing important clinical value.

Blood lipids in patients with high and low physical activity depending on polymorphism of beta-2 and 3-adrenergic receptor genes

Background. The aim of the study was to investigate the lipid levels in patients with various physical activity and polymorphous variants of ADRB2 (Gln27Glu and Arg16Gly) and ADRB3 (Trp64Arg) genes. Material and methods. One hundred and fifty subjects were enrolled in the study; mean age was 44.7 ± 8.9 y.o. Physical activity was assessed using Omron Walking style III step counter HJ-203-EK pedometer. Lipids were assessed via enzymatic method using Cormay reagent kit (Poland). Genotyping of polymorphous sites of ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713) and ADRB3 (Trp64Agr, rs4994) genes was performed using SNP-express-SHOT reagent kits manufactured by Litex Research and Production Company, via real-time polymerase chain reaction. Results. Individuals walking more than 5000 steps daily with Gly16Gly polymorphism had significantly higher blood lipids. Total cholesterol (TC), triglycerides, LDL and HDL-cholesterol levels were 5.10 (3.86–5.74), 1.13 (0.66–1.51), 3.28 (2.14–3.70), 1.43 (1.32–1.63) mmol/L in Arg16 group and 5.55 (5.23–6.96), 1.56 (0.45– –2.02), 3.87 (3.09–4.46) and 1.30 (1.13–1.68) mmol/L in Gly16Gly group. The differences in lipid parameters were established for polymorphous variants of ADRB3 gene in patients walking more than 5000 steps daily. In Trp54 carriers, TC, triglycerides, LDL and HDL-cholesterol levels were 5.23 (4.00–5.69), 1.25 (0.80–1.56), 3.25 (2.22–3.80) and 1.41 (1.26–1.53) mmol/L, respectively. In 54Arg carriers group, lipids were significantly higher: TC 5.74 (5.59–6.88), triglycerides 1.51 (1.03–1.90), LDL-cholesterol 3.78 (3.38–5.06) and HDL-cholesterol 1.68 (1.13–1.81) mmol/L. Conclusion. This analysis suggests that carriers of Arg16 of ADRB2 gene and/or Trp54 of ADRB3 gene tend to have lower lipid parameters when they have high physical activity (walking more than 5000 steps a day) in comparison to carriers of 16Gly and/or 54Agr. There is no association between lipids level and ADRB2 (Gln27Glu and Arg16Gly) and ADRB3 (Trp64Agr) polymorphisms when individuals have low physical activity (walking less than 5000 steps a day).

ADRB2 polymorphism Arg16Gly modifies the natural outcome of heart failure and dictates therapeutic response to \u03b2-blockers in patients with heart failure

We sought to investigate the association of single nucleotide polymorphisms (SNPs) of the genes involved in βAR signaling with the response of patients to βAR blockers. A total of 2403 hospitalized patients with chronic heart failure (HF) were enrolled in a multicenter observational study as the first cohort and followed up for a mean period of 20 months. Genes for β1AR, β2AR, and the major cardiac G-protein-coupled receptor kinases (GRKs) GRK2 and GRK5 were analyzed to identify SNPs, and patients were stratified according to genotypes. A second independent cohort enrolling 919 patients with chronic HF was applied to validate the observed associations. The signaling properties of the key identified SNPs were assessed in vitro. Our data showed that HF patients harboring the Gly16 allele in the gene for β2AR (ADRB2) had an increased risk of the composite end point relative to patients who were homozygous for Arg16. Notably, these patients showed a beneficial response to βAR-blocker treatment in a G allele-dose-dependent manner, whereas Arg16 homozygotes had no response to βAR-blocker therapy. This Arg16Gly genotype-dependent heterogeneity in clinical outcomes of HF was successfully validated in the second independent population. Besides, the in vitro experiments revealed that G allele carriers were defective in β2AR-coupled inhibitory adenylate cyclase g (Gi) protein signaling.

Association between cholesterol changes and PPRG, ADRB2 and ADRB3 polymorphism during lifestyle modification programme in obese patients

Association between cholesterol changes and PPRG, ADRB2 and ADRB3 polymorphism during lifestyle modification programme in obese patients

MRNA expression profile in peripheral blood mononuclear cells based on ADRB1 Ser49Gly and Arg389Gly polymorphisms in essential hypertension - a case-control pilot investigation in South Indian population.

β1-Adrenoreceptor (ADRB1) genetic polymorphisms are widely studied for susceptibility to many cardiovascular diseases such as essential hypertension. However, the mRNA expression of ADRB1 is rarely studied. A case-control pilot study with 292 hypertensives and 324 controls was designed to evaluate the role of the Ser49Gly and Arg389Gly, which are commonly studied single nucleotide polymorphisms (SNP), in the mRNA levels of ADRB1, in conjunction with its genetic predisposition to essential hypertension. Differential expression of ADRB1 mRNA was seen between hypertensives and controls (p<0.01) based on genetic variants of Ser49Gly. Among hypertensive subjects, Ser49Ser and Gly49Gly were highly expressed in comparison to Ser49Gly (p<0.05 and p<0.01, respectively), whereas genetic variants of Arg389Gly did not demonstrate any such variations. We found no association between the ADRB1 SNPs viz., Ser49Gly and Arg389Gly and essential hypertension. The increased mRNA levels of Gly49Gly may indicate a plausible role in the interindividual variations in drug response. Further, ADRB1 polymorphisms did not contribute to the genetic risk of essential hypertension. Studies with larger sample size are warranted to confirm these observations in the South Indian population.

ADRB3 polymorphism rs4994 (Trp64Arg) associates significantly with bodyweight elevation and dyslipidaemias in Saudis but not rs1801253 (Arg389Gly) polymorphism in ARDB1

BackgroundIn some populations, obesity and body weight related disorders show a correlation with polymorphisms in three subtypes of beta-adrenoceptor (β1, β2, and β3) [ADRB1, ADRB2 and ADRB3] genes. We scanned for the polymorphism of Arg389Gly (rs1801253) in ADRB1 and Trp64Arg (rs4994) in ADRB3 genes in Saudi population to determine association, if any, of these polymorphisms with obesity and related disorders.MethodsWe studied 329 non-related adults (33.1% men and 66.9% women), aged 18–36 years. Anthropometric measurements were recorded, and Body mass index (BMI) and waist/hip ratio were calculated; leptin, insulin, lipidogram, and glucose concentrations were determined. ADRB1 and ADRB3 polymorphisms (Arg389Gly and Trp64Arg, respectively) were screened by DNA sequencing. The subjects were divided into three groups according to BMI: normal weight (BMI < 25 kg/m2), overweight (BMI ≥25.1–29.9 kg/m2) subjects, and obese (≥30 kg/m2).ResultsIn the age-matched groups of the normal weight, overweight and obese male and female subjects, all anthropometric parameters were found to be significantly higher, and in the obese group, all biochemical parameters were significantly elevated compared to the normal weight controls. The allelic frequency of Gly389 ADRB1 did not differ amongst the three groups, whereas the frequency of Arg64 of ADRB3 gene was significantly higher in the overweight and obese subjects, compared with the normal weight subjects. In addition, subjects carrying Arg64 allele regardless of their BMI had a greater waist and hip circumference, W/H ratio, plasma cholesterol, triglyceride, LDL, leptin, insulin, and glucose level compared to those with the wild-type Trp allele.ConclusionThe results of this study have shown a significant association between the Trp64Arg polymorphism in ADRB3 gene and the development of overweight and obesity in Saudi populations. It also has an influence on the levels of lipid, insulin, leptin, and glucose, whereas, Arg389Gly polymorphism in ADRB1 is not associated with overweight, obesity or dyslipidaemias in Saudis.

A functional SNP upstream of the ADRB2 gene is associated with COPD.

BackgroundPrevious studies have suggested that β2-adrenergic receptor (ADRB2) is associated with COPD. However, the role of genetic polymorphisms in ADRB2 on COPD has not been evaluated yet.MethodsIn this study, SNaPshot genotyping, luciferase assay, chromatin immunoprecipitation and real-time polymerase chain reaction were adopted to investigate the association between ADRB2 genetic polymorphisms and COPD, comprehensively.ResultsOne single nucleotide polymorphism (rs12654778), located upstream of ADRB2, showed a significant association with COPD by the logistic regression analysis after adjusting for age, sex and smoking history (p=0.04) in 200 COPD patients and 222 controls from southwest Chinese population. Furthermore, the luciferase assay indicated that rs12654778-A allele reduced the relative promoter activity by ~26% compared with rs12654778-G allele (p=0.0034). The chromatin immunoprecipitation analysis demonstrated that rs12654778 modulated the binding affinity of transcription factor neurofibromin 1. In addition, a significantly reduced expression of ADRB2 in COPD patients was observed, compared with normal controls (p=0.017).ConclusionOur findings suggest a previously unknown mechanism linking allele-specific effects of rs12654778 on ADRB2 expression to COPD onset, for the first time.