Beta3-adrenergic Receptor Gene Research Articles

Trp64Arg polymorphism of the ß₃-adrenergic receptor and its association with obesity in the young population of North Macedonia

The pandemic surge of obesity is becoming a concern for civilization. Genetic factors play an important role in obesity. The polymorphism of the beta3-adrenergic receptor gene (ADRB3), whose protein is located mainly in adipose tissue, has been associated with body weight disorders and obesity. The relationship between the ADRB3 polymorphism and BMI has been controversial. Our research examines the impact of the Trp64Arg polymorphism in the ADRB3 gene on anthropometric and biochemical parameters. Analyzing data from 110 young North Macedonians, we employed PCR-RFLP genotyping alongside biochemical and anthropometric assessments. Obesity was measured using the body mass index (BMI), and weight groups were determined according to World Health Organization (WHO) guidelines. Significant associations emerged between ADRB3 genotypes and crucial biochemical parameters-glucose, triglyceride, and cholesterol levels. P-values of 0.013, 0.011, and 0.025, respectively, indicate a potential correlation between specific genotypes and variations in these metabolic markers. This pioneering study sheds light on ADRB3's role in metabolic health, offering potential for personalized interventions and emphasizing the need for further research in the North Macedonian population.

DIAGNOSIS OF FIBROMYALGIA IN HEALTH PRACTICE

Fibromyalgia is a chronic non inflammatory, non-autoimmune central afferent processing disorder leading to a diffuse pain syndrome. It affects individuals of different age groups, sex and sociocultural background. It is estimated to affect 2-5% of western population. The symptoms include widespread pain, fatigue, stiffness and sleep disturbance, cognitive problems and mood disorders (anxiety, depression or both) 1. The etiology of Fibromyalgia (FM) is unknown; however several factors may contribute to development as well as severity of symptoms of FM. Genetic polymorphisms have been reported in serotonin transporter and receptors, as well as in dopamine, beta2 adrenergic and glutamate receptor genes. 2 Middle aged women and young are more affected. Sleep abnormalities, autonomic dysregulation, and psychological variables like perfectionist personality, negative beliefs, low self-esteem, depression and anxiety are the contributory factors.3 Physical examination and pathological investigations reveal no evidence of articular, osseous or soft tissue inflammation or degeneration. Patients may have tender points both above and below the waist. The previously followed criteria, depending on presence of tender points, are no more followed. In 2010, a new diagnostic criterion was adopted by American College of Rheumatology (ACR) 4. It has three points: - 1. Widespread pain index (WPI)>7 & a symptom severity (SS) score >5 or widespread pain index 3-6 & (SS) score >9. 2. Symptoms present for at least 3.No other disorder to explain In differential diagnosis, many diseases need to be ruled out making the diagnosis of FM. These are systemic lupus erythematosis, systemic sclerosis, polymyositis, ankylosing spondylitis, osteomalacia, rheumatoid arthritis, polymyalgia rheumatic hypothyroidism, chronic hepatitis, HIV, hemo- chromatosis, celiac disease, myasthenia gravis, hyperthyroidism, myopathies, Sjogren`s, adrenal insufficiency, lymphoma and chronic fatigue syndrome.5 Although the exact pathophysiology of FM is unknown, most of the researchers believe that the pathophysiology of FM is due to the central sensitization within the CNS, manifesting as amplified pain perception. The specific abnormalities that have been observed in the afferent pain procession areas of the CNS in FM patients, who exhibit the following symptoms: increased excitability of dorsal horn nuclei due to abnormal windup; increased levels of substance P, nerve growth factor, glutamate and aspartate measured in CSF of patients with FM 6expanded receptive fields for central pain perception (central sensitization); MRI shows expanded fields in the insula, anterior cingulate cortex and somatosensory area.7 The abnormalities within the descending analgesia system are also observed i.e decreased levels of pain inhibitory neurotransmitters including nor epinephrine, serotonin, dopamine and suppression of normal activity of dopamine releasing neurons in limbic system.1 The management of FM is very challenging. It has many components i.e patient education, physical exercises, analgesia, treatment of associated condition like anxiety, depression, and mood disorders. Counseling about the disease and CBT are also helpful. Medication approved for the treatment of FM are: Serotonin-noreprenphine reuptake inhibitors (SNRIs); Duloxetine ,venlaxafine, Milnacipran. Anticonvulsants; Pregabalin. Tri cyclic antidepressants: Amitriptyline, imipramine. Analgesia; Tramadol. Paracetamol and NSAIDS are not affective for analgesia.8,9 The diagnosis of FM is quiet challenging in the developed world with good evaluation and referral system. In underdeveloped country with poor medical education and no referral system FM patients are the mostly go un-diagnosed and hence are under treated. It is high time to highlight the importance of diagnosis of FM by the general practitioner and other specialties doctors for proper management of these patients. The disease impact of FM is not less than any other chronic inflammatory disease like Rheumatoid Arthritis. On an average the FM patients visit doctor 3-4 times more often than the general population (17 versus 4 visits/year). The frequent visits of patients with FM, is one of the factors of increasing burden on health system as well as having socio-economic impact on patients.

Study of the polymorphism of the ADRB2 molecular structure and its influence on the development of chronic postsurgical pain in children

Introduction. Pain is a signal to any aggression that leads to cellular damage and requires a defensive response. Uncontrolled acute perioperative visceral pain can lead to the development of pain chronicity. By studying the characteristics of chronic pain, some scientists have identified relationships with single-nucleotide polymorphisms of the beta2-adrenergic receptor (ADRB2) gene. Purpose - to study the dependence of pain expression in the postoperative period in children on the polymorphism of the molecular structure of the ADRB2 receptor. Materials and methods. The study involved 42 children (20 boys and 22 girls) aged 7 to 18 years who were treated in the surgical department in 2020-2022 for acute appendicitis and peritonitis. Results. Based on the results of examining all the subjects under study, 13 children had the Arg16Gly polymorphism, 15 children had the Arg16Gly polymorphic variant, and 14 children were diagnosed with the homomorphic Gly16Gly polymorphism in the ADRB2. The data obtained confirmed the trend of the preliminary analysis and proved better body response to pain relief and reduced pain intensity in individuals with the Arg16Arg variant of the ADRB2. Analysis of the dependence between the polymorphism of the ADRB2 molecular structure and Visual Analogue Scale (VAS) scores in children in the postoperative period proved that the presence of Arg in the receptor phenotype had a strong negative correlation with the VAS score on discharge day (r=-0.822, p<0.001), while the presence of Gly in the receptor phenotype had a strong positive correlation with the Visual Analogue Scale score on discharge day (r=0.814, p<0.001). In regression analysis, the presence of Gly in the receptor phenotype was associated with a 1.917-fold increase in the VAS score at hospital discharge (OR: 1.917; 95% CI: 1.448-2.385; р<0.001). Conclusions. The presence of the homomorphic Arg16Arg variant of the ADRB2 in children who underwent anterior abdominal wall surgery was accompanied by rapid response to analgesics. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

De Novo BETA-2 adrenergic receptor gene variant associated with obesity

Abstract Introduction Obesity is a known condition when the energy taken is more than the energy consumed. According to the World Obesity Atlas data, 1 out of every five women and 1 out of every seven men will live with obesity by 2030.The prevalence of obesity was 21.1% in Turkey (2019). Although environmental factors and changes in dietary patterns are essential in this increase, genetic factors also have an effect. Mutations in genes that affect catecholamine function, which play an essential role in energy consumption and lipolysis, also lead to obesity. One of these critical genes is the β2-adrenergic receptor gene (ADRB2). It was previously reported that it is responsible for regulating lipolysis and thermogenesis and is mainly expressed in the adipose tissues. This gene induces catecholamine activation and leads to lipid mobilization in adipose tissue. Clinical Case A 25-year-old male patient applied to our outpatient clinic with obesity, sexual dysfunction. The patient had been overweight since childhood and did not use any medication at admission. On physical examination, his body mass index:50.8 kg/cm2.and has only hair on the genital area and axilla. His parents are consanguineous, and his mother, father, and brother are also obese. He had diabetes mellitus, hypolipidemia, hypogonadotropic hypogonadism, and GH deficiency in his initial tests (Table-1). The other pituitary hormones were usual. There was not any pathology in the pituitary and brain magnetic resonance images. LHRH test result was interpreted as hypothalamic dysfunction. The insulin hypoglycemia test was performed due to growth hormone deficiency to accurate to GH deficiency. Clinic exome sequencing was performed on the patient, and a de novo heterozygous mutation in the ADRB2 gene was detected, which has a role in lipolysis, and thermogenesis and hence is important for obesity. Two more mutations were identified that related to thyroid functions. The DUOX2 gene variant has an association with thyroid dyshormonogenesis, and the IRS4 gene variant has a role in hypothyroidism. Further studies are needed to identify the pathogenicity of variants. Molecular identification of mutations has important implications for personalized medicine, including genetic counseling and the development of specific treatment protocols. We started the patient with exenatide 10 mg/day, metformin 2000 mg/day, testosterone propionate, and a diet program. Conclusion Studies show that low ADRB2 expression increases the risk of obesity. Obesity is increasing rapidly over time globally, and it is necessary to know the underlying pathophysiologies and genetic etiologies and to develop new treatment algorithms for this in order to reduce mortality and morbidity. Therefore, gene mutations underlying obesity, the metabolic changes it causes, environmental factors, and diet should be considered. Considering the scarcity of available anti-obesity drugs, understanding the genetic makeup may be influential in developing new therapeutic targets.

Association Between Trp64Arg Polymorphism of Beta-3 Adrenergic Receptor Gene and Susceptibility to Overactive Bladder: A Meta-Analysis

Objective: Some studies have been carried out to investigate the association between Trp64Arg polymorphism in beta-3 adrenergic receptor gene (ADRB3) and susceptibility to overactive bladder (OAB), but the results remain inconsistent. We carried out a meta-analysis to acquire a more accurate estimation. Methods: All eligible studies were searched in PubMed, Web of Science, Embase, and Cochrane Library. Pooled odds ratios, with 95% confidence intervals, were assessed for the association using fixed and random effects models. Results: The overall results of this meta-analysis demonstrated that there might be an association between Trp64Arg polymorphism and susceptibility to OAB in allele model, dominant model, and heterozygote comparison with a relative risk of 2.00 (95% CI 1.36–2.93), 2.13 (95% CI 1.20–3.76), and 2.07 (95% CI: 1.13–3.79), respectively. However, in the recessive model and homozygote comparison, no significant association between ESR1 Trp64Arg polymorphism and susceptibility to OAB was observed, with a relative risk of 2.47 (95% CI 0.63–9.73) and 3.12 (95% CI: 0.79–12.35), respectively. Based on trail sequential analysis, the results turned out to be true positive in the allele model, false positive in the dominant model and heterozygote comparison, and negative in the recessive model and homozygote comparison, respectively. Conclusion: Our analysis indicated that Trp64Arg polymorphisms in ADRB3 might increase the risk of OAB twice in the allele model, but further well-designed studies with large sample sizes are required to confirm the present findings in other modes and comparisons.

Effect of Beta 2-Adrenergic Receptor Gly16Arg Polymorphism on Taste Preferences in Healthy Young Japanese Adults.

The Gly16Arg polymorphism results in a G to C nucleotide mutation in the human beta 2-adrenergic receptor (ADRB2) gene and has a relationship with obesity; however, this substitution’s effects on food preferences are unclear. Therefore, we determined this relationship among healthy young adults (mean age, 23.4; n = 52). To evaluate food preferences, four categories of food (sweet, salty, sour, and bitter) along with high-fat foods were evaluated using a self-reporting questionnaire. Male (n = 26) and female subjects (n = 26) were genotyped for the polymorphism and further divided into three groups (two homozygous groups, GG, CC; and a heterozygous group, GC). Preference for sour foods in the GG group was higher compared with that in the CC group in females (p < 0.05). When sweet foods were classified into low- and high-fat subgroups, preference for high-fat sweet foods in the GG group was higher than that for low-fat sweet foods in all subjects (p < 0.05). The degree of preference for high-fat foods in the GG group was higher than other groups for males (p < 0.05). These results suggest that ADRB2 polymorphism is associated with food preference. Understanding the relationship of ADRB2 substitution to food preference will be valuable for designing individualized anti-obesity strategies.

Differential Effect of Fat Intake on Blood Pressure in Healthy Japanese Women with and without the Variant of Fat Mass and Obesity-Associated Gene.

A high-fat diet is believed to be a risk factor for hypertension through inducing obesity. It has been reported that variants of the fat mass and obesity-associated (FTO) and beta-3 adrenergic receptor (B3AR) genes are associated with obesity and blood pressure. The purpose of this study was to investigate the effect of dietary fat on blood pressure with or without the variant of the FTO and B3AR genes. A total of 227 healthy Japanese women aged 18 to 64 years were recruited for measurement of nutrient intake and blood pressure. The single nucleotide polymorphism rs9939609 of the FTO gene and rs4994 of the B3AR gene were genotyped. Spearman's rank correlation coefficient was applied to investigate the relationship between fat intake and blood pressure. A hierarchical multiple regression analysis was performed to determine whether the genotype interacts with fat intake to affect blood pressure. No significant correlations were found between fat intake and either systolic or diastolic blood pressure. A significant negative correlation was found between fat intake and both blood pressures in the FTO-gene-variant group, but not in the normal-FTO-gene group. In hierarchical multiple regression analysis, the interaction of fat intake and the gene variant showed significance, and the change in coefficient of determination (R 2) was significantly increased with increases of the interaction variable. These results indicate that the effect of fat intake on blood pressure may be modified by the variant of the FTO gene such that a high-fat diet intake may be associated with a decrease of systolic and diastolic blood pressure in healthy Japanese women with the FTO variant. Our results did not support the hypothesis that a high-fat diet increases blood pressure.

Beta-2 Adrenergic Receptor Gene Expression in HER2-Positive Early-Stage Breast Cancer Patients: A Post-hoc Analysis of the NCCTG-N9831 (Alliance) Trial

BackgroundBeta-2 adrenergic receptor (ß2AR) modulates immune activation and may enhance trastuzumab activity. We assessed the impact of ß2AR gene (ADRB2) expression on the outcomes of patients with HER2-positive early-stage breast cancer enrolled on the NCCTG-N9831 trial. Patients and MethodsThis is a post-hoc analysis of the NCCTG-N9831 trial, which compared chemotherapy (arm A) versus chemotherapy plus trastuzumab (arms B&C) as adjuvant treatment of patients with HER2-positive early-stage breast cancer, with disease-free survival (DFS) as primary endpoint. Gene expression levels retrieved by DASL assay were used to classify patients as ADRB2-high or ADRB2-low. Hazard ratios (HRs) were calculated by a Cox proportional model adjusted for prognostic variables and ADRB2 expression. Correlations between ADRB2 expression and stromal tumor-infiltrating lymphocyte (TIL) levels were assessed with Pearson coefficient. A multivariable Cox regression model with interaction term was performed to assess the interaction between ADRB2 expression and treatment arm; and ADRB2 expression and a 8-gene signature previously shown to predict trastuzumab benefit. ResultsOverall, 1,282 patients were included (ADRB2-high [N = 944] / ADRB2-low [N = 338]). A high expression of ADRB2 was associated with a longer DFS (P = .01) in the overall population. The addition of trastuzumab to chemotherapy improved DFS only in patients with ADRB2-high tumors (P < .01). ADRB2 expression was correlated with TIL levels (r = 0.24, P < .001). No association between ADRB2 expression and the 8-gene trastuzumab benefit signature was observed (P = .32). ConclusionOur findings suggest that a high ADRB2 expression is a favorable prognostic factor and may identify patients with HER2-positive early-stage breast cancer who benefit from adjuvant trastuzumab. Trial Registrationclinicaltrials.gov NCT00005970

Identification of polymorphisms in the MSTN and ADRB3 genes associated with growth and ultrasound carcass traits in Kajli sheep

The aim of this investigation was to find single nucleotide polymorphisms (SNPs) in the myostatin (MSTN) and the beta-3 adrenergic receptor (ADRB3) genes associated with growth and ultrasound carcass traits in Kajli sheep. The five growth traits were birth weight (BWT-EBV), 120-day weight (120DWT-EBV), 180-day weight (180DWT-EBV), 270-day weight (270DWT-EBV), and 365-day weight (365DWT-EBV). The three ultrasound carcass traits were width (WLD) and depth of longissimus dorsi (DLD) and back fat thickness (BFT). The analysis of the MSTN sequence revealed one non-synonymous substitution (c.197T > A) in exon 1, one single nucleotide substitution (c.373 + 18G > T) in intron 1, and one synonymous substitution (c.861T > A) in exon 3. However, there were four single nucleotide synonymous substitutions (c.130C > T, c.294C > G, c.579G > T, and c.654C > G) in exon 1 of the ADRB3 gene. All the SNPs in the MSTN gene, except for c.373 + 18G > T, were in Hardy-Weinberg Equilibrium (HWE). Conversely, none of the SNPs found in ADRB3 were in HWE. Two of the MSTN SNPs (c.197T > A and c.373 + 18G > T) had significant associations with all evaluated growth and ultrasound carcass traits. The SNPs c.130C > T and c.294C > G in ADRB3 were significantly associated with 180DWT-EBV. Collectively, these findings indicate that several SNPs in the studied genes were significantly related to growth and carcass traits in Kajli sheep.

A network pharmacology approach to explore the potential role of Panax ginseng on exercise performance

[Purpose]As Panax ginseng C. A. Meyer (ginseng) exhibits various physiological activities and is associated with exercise, we investigated the potential active components of ginseng and related target genes through network pharmacological analysis. Additionally, we analyzed the association between ginseng-related genes, such as the G-protein-coupled receptors (GPCRs), and improved exercise capacity.[Methods]Active compounds in ginseng and the related target genes were searched in the Traditional Chinese Medicine Database and Analysis Platform (TCMSP). Gene ontology functional analysis was performed to identify biological processes related to the collected genes, and a compound-target network was visualized using Cytoscape 3.7.2.[Results]A total of 21 ginseng active compounds were detected, and 110 targets regulated by 17 active substances were identified. We found that the active compound protein was involved in the biological process of adrenergic receptor activity in 80%, G-protein-coupled neurotransmitter in 10%, and leucocyte adhesion to arteries in 10%. Additionally, the biological response centered on adrenergic receptor activity showed a close relationship with G protein through the beta-1 adrenergic receptor gene reactivity.[Conclusion]According to bioavailability analysis, ginseng comprises 21 active compounds. Furthermore, we investigated the ginseng-stimulated gene activation using ontology analysis. GPCR, a gene upregulated by ginseng, is positively correlated to exercise. Therefore, if a study on this factor is conducted, it will provide useful basic data for improving exercise performance and health.

Abstract MP26: Angiotensin-(1-7) Increases Vascular Beta-2 Adrenergic Receptor Expression In Aging Mice

Aging is associated with increased sympathetic tone, which desensitizes vascular beta-2 adrenergic receptors (B2AR) to impair vasodilation and promote hypertension. We recently demonstrated that chronic treatment with angiotensin (Ang)-(1-7), a protective hormone of the renin-angiotensin system, decreases blood pressure and cardiac sympathetic tone in aging mice. In this study, we hypothesized that sympathoinhibitory effects of Ang-(1-7) would restore vascular B2AR expression to lower blood pressure in aging. To test this, aging (16-month-old) and young (2-month-old) male C57BL/6J mice received Ang-(1-7) [400 ng/kg/min, n=4] or saline (n=4) infusion for 6 weeks via subcutaneous osmotic mini-pump. At end of treatment, alpha- and beta-adrenergic receptor gene expression was measured in mesenteric arteries, thoracic aorta, and cardiac tissue by quantitative real-time PCR and quantified with 2-ΔΔCT methods. In a separate experiment, male C57BL/6J mice received a single subcutaneous injection of Ang-(1-7) (2 mg/mg, n=4), saline (n=3), or the B2AR antagonist ICI 118,551 (1 mg/kg) plus Ang-(1-7) (n=3). Blood pressure was measured via a carotid artery catheter at baseline and post-treatment. We found that aging mice have decreased mesenteric B2AR gene expression, which was restored by Ang-(1-7) (young saline: 1.04±0.35; aged saline: 0.46±0.17; aged Ang-(1-7): 1.04±0.31 A.U., p=0.026). As a control, Ang-(1-7) did not induce significant changes in B2AR mRNA in thoracic aorta or cardiac tissue, or changes in other adrenergic receptor subtypes (alpha1 or beta1) in any of the tissues studied in aging mice (p&gt;0.05). We further found that depressor effects of acute Ang-(1-7) in mice are attenuated by B2AR blockade (saline: Δ -11±4 mmHg; Ang-(1-7): Δ -26±3 mmHg; ICI 118,551+Ang-(1-7): Δ -4±4 mmHg, p=0.009). Overall, these findings suggest that Ang-(1-7) restores B2AR expression in mesenteric resistance vessels in aging mice, and depressor effects of acute Ang-(1-7) are partially mediated by B2AR. These data support the concept that Ang-(1-7) decreases blood pressure in aging by restoring B2AR-mediated vasodilation. More broadly, Ang-(1-7) may provide a novel treatment target for age-related hypertension and cardiovascular disease.

Alpha-2 beta-adrenergic receptor (301-303 I/D) gene polymorphism in hypertension and type 2 diabetes mellitus diseases among Saudi cases in the Qassim region.

The hypertension (HTN) and type 2 diabetes mellitus (T2DM) are a common multifactorial disease due to genetics and environmental factors. The alpha 2B adrenergic receptor (α2B-AR) has relationship with secretion of insulin and mediates the vasoconstriction that elevate blood pressure. This study aimed to determine the association between α2B-AR gene polymorphism with HTN and T2DM in Saudi cases. 200 cases and 100 healthy controls from Saudi population were recruited from the Internal Medicine clinic, Qassim University. The patients were grouped into: 72 HTN without T2DM; 62 HTN with T2DM and 66 T2DM only. Full medical history, examination and biochemical assays were performed for all participants. Genomic DNA was isolated from blood lymphocytes of all subjects for detection of α2B-AR gene polymorphism by using polymerase chain reaction (PCR). The results found a significant association between D carriers genotype and HTN with T2DM cases (p < 0.05) as well as with T2DM-only cases, (p < 0.05) compared to control. Regardless of HTN status, only cases with HTN and T2DM as well as those with T2DM were significantly associated with the recessive model DD versus II+ID (p < 0.05). So, D carriers genotype was significantly associated with total cases of HTN and T2DM (p < 0.05) compared to controls. Our results suggested that there is a relationship between the α2B-AR I/D gene polymorphism and the risk for T2DM with or without HTN, but no such comparable relationship is evident with HTN-only cases among Saudi population in Qassim region.

Correlations of Three Polymorphisms in Beta2-Adrenergic Receptor Gene with Chronic Obstructive Pulmonary Disease Risk and Related Phenotypes: A Meta-Analysis

IntroductionThe gene encoding β2-adrenergic receptor (ADRB2) is a candidate gene for chronic obstructive pulmonary disease (COPD), yet the results are not often reproducible. We aimed to assess the association of ADRB2 genetic polymorphisms (rs1042713, rs1042714, and rs1800888) with COPD risk and COPD-related phenotypes via a meta-analysis.Material and methodsLiterature search, quality evaluation, and data extraction were completed independently and in duplicate. Effect-size estimation is expressed as odds ratio (OR) or weighted mean difference (WMD) with 95% confidence interval (CI).ResultsTotal 15 articles were meta-analyzed, including 12 articles (2917/8807 patients/controls) for COPD risk, and 6 articles (18350 subjects) for COPD-related phenotypes. Overall, there was no detectable significance for the association of rs1042713 (OR, 95% CI: 1.02, 0.88-1.19) and rs1042714 (1.01, 0.85-1.20) with COPD risk, and only marginal significance retained for rs1800888 (1.31, 1.00-1.72). In subsidiary analyses, the association of rs1042713 and rs1042714 with COPD risk was significant in populations of Asian origin (OR: 1.66 and 1.351, 95% CI: 1.13-2.44 and 1.02-1.79). Additionally, carriers of rs1042713 AA genotype had significantly lower levels of FEV1 (WMD, 95% CI: -0.011 L, -0.026 to -0.004) than carriers of GG genotypes, and FVC% predicted levels were significantly increased for the comparisons of rs1042713 AA genotype (6.914, 4.829 to 8.999) and AG genotype (4.249, 2.925 to 5.573) with GG genotype. There were low probabilities of publication bias.ConclusionsOur findings suggest that contribution of ADRB2 genetic polymorphisms to COPD risk is small and ethnicity-dependent, and to COPD-related phenotypes is significant.

Investigation Trp64Arg polymorphism of the beta 3-adrenergic receptor gene in nonobese women with polycystic ovarian syndrome.

BackgroundPolycystic ovary syndrome (PCOS) is a multifactorial and heterogeneous disease that has a potent inheritable component based on familial clustering. Despite many studies in the genetic field of PCOS, the genes that are involved in the causes of this syndrome have not been thoroughly investigated.Objective The purpose of this study was to establish the occurrence of the Trp64Arg polymorphism of beta3 adrenergic receptor in non-obese women with PCOS.Materials and MethodsThis cross-sectional study was performed on 100 women with PCOS and normal women as the control group in Imam Khomeini Hospital of Tehran in 2016-2017. Peripheral blood sample (2 cc) was obtained from two groups for genomic DNA based on the gene bank. Polymorphisms were genotyped by of using ADRB3 Trp64Arg. Then the DNA was extracted by genomic kiagen kit. The primer was analyzed for PCR based on gene bank by using Primer3 software and then confirmed by primer Blast tool at NCBI site to conformity to the beta-3 adrenergic receptor gene. The protein changes were assessment by the Clastal W software.ResultsThe sequence analysis presented in NCBI, transcript variant 1, with the code NM_000025.2, shows changes in the amino acid sequence of exon 1 in women with PCOS. Polymorphism in the codon 64 encoding the amino acid tryptophan (W) occurred in the nucleotide c.T190C, which changed the nucleotide T to C and then the amino acid sequence of the tryptophan was altered to arginine pW64R.Conclusion T-C polymorphism is evident in the codon 64 of the adrenergic β3 receptor in patients with PCOS. Therefore, Beta3 adrenergic receptor gene polymorphism (Thr164Ile) associates with this syndrome in nonobese women.

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 gene of sinonovacula constricta and its functions in damage healing of tissue

Beta-2 adrenergic receptor is a G protein coupled receptor, which is closely related to biological activities such as growth, endocrine and metabolism. The sequence of beta-2 adrenergic receptor was screened from the transcriptional library of the razor clam Sinonovacula constricta, and the full-length sequence of beta-2 adrenergic receptor was obtained by PCR and RACE technology, named as ScADRB2. The cDNA length of ScADRB2 was 1 497 bp, including 148 bp 5' untranslated region, 191 bp 3' untranslated region, and 1 158 bp open reading frame, encoding 385 amino acids. Primers were designed in ORF to detect the expression level in hemolymph,liver, waterpipe, foot, mantle, gill, and gonad, by quantitative real-time PCR, respectively. The results showed that the expression of ScADRB2 was the highest in the mantle, relatively high in the foot, lower in the siphon and gonad, but the lowest in the hemolymph, liver and gills. Tissue injury experiment was designed and the samples were collected at 8 h, 24 h, 48 h, 60 h and 72 h after injuring siphon. The results showed that the expression level of ScADRB2 was higher at 8 h and 24 h, decreased significantly at 36 h, increased at 48 h, and decreased at 60 h or 72 h. The results showed that beta-2 adrenergic receptor might be involved in the process of damage and repair of S. constricta.

Modified constraint-induced movement therapy alters synaptic plasticity of rat contralateral hippocampus following middle cerebral artery occlusion.

Modified constraint-induced movement therapy is an effective treatment for neurological and motor impairments in patients with stroke by increasing the use of their affected limb and limiting the contralateral limb. However, the molecular mechanism underlying its efficacy remains unclear. In this study, a middle cerebral artery occlusion (MCAO) rat model was produced by the suture method. Rats received modified constraint-induced movement therapy 1 hour a day for 14 consecutive days, starting from the 7th day after middle cerebral artery occlusion. Day 1 of treatment lasted for 10 minutes at 2 r/min, day 2 for 20 minutes at 2 r/min, and from day 3 onward for 20 minutes at 4 r/min. CatWalk gait analysis, adhesive removal test, and Y-maze test were used to investigate motor function, sensory function as well as cognitive function in rodent animals from the 1st day before MCAO to the 21st day after MCAO. On the 21st day after MCAO, the neurotransmitter receptor-related genes from both contralateral and ipsilateral hippocampi were tested by micro-array and then verified by western blot assay. The glutamate related receptor was shown by transmission electron microscopy and the glutamate content was determined by high-performance liquid chromatography. The results of behavior tests showed that modified constraint-induced movement therapy promoted motor and sensory functional recovery in the middle cerebral artery-occluded rats, but had no effect on cognitive function. The modified constraint-induced movement therapy upregulated the expression of glutamate ionotropic receptor AMPA type subunit 3 (Gria3) in the hippocampus and downregulated the expression of the beta3-adrenergic receptor gene Adrb3 and arginine vasopressin receptor 1A, Avpr1a in the middle cerebral artery-occluded rats. In the ipsilateral hippocampus, only Adra2a was downregulated, and there was no significant change in Gria3. Transmission electron microscopy revealed a denser distribution the more distribution of postsynaptic glutamate receptor 2/3, which is an α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor, within 240 nm of the postsynaptic density in the contralateral cornu ammonis 3 region. The size and distribution of the synaptic vesicles within 100 nm of the presynaptic active zone were unchanged. Western blot analysis showed that modified constraint-induced movement therapy also increased the expression of glutamate receptor 2/3 and brain-derived neurotrophic factor in the hippocampus of rats with middle cerebral artery occlusion, but had no effect on Synapsin I levels. Besides, we also found modified constraint-induced movement therapy effectively reduced glutamate content in the contralateral hippocampus. This study demonstrated that modified constraint-induced movement therapy is an effective rehabilitation therapy in middle cerebral artery-occluded rats, and suggests that these positive effects occur via the upregulation of the postsynaptic membrane α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor expression. This study was approved by the Institutional Animal Care and Use Committee of Fudan University, China (approval No. 201802173S) on March 3, 2018.

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.

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

A single-nucleotide polymorphism of the beta 2-adrenergic receptor gene can predict pathological complete response to taxane- and platinum-based neoadjuvant chemotherapy in breast cancer.

BackgroundGermline genetic polymorphisms in certain genes are associated with the response to anthracycline- and taxane-based neoadjuvant chemotherapy in breast cancer (BC). This translational study aims to evaluate the potential role of rs1042713 in the beta 2-adrenergic receptor (ADRB2) gene in predicting pathological complete responses (pCRs) to taxane- and platinum-based neoadjuvant chemotherapy in locally advanced breast cancer (LABC).Materials and methodsThe distribution frequencies of rs1042713 were genotyped in LABC patients who received taxane- and platinum-based neoadjuvant chemotherapy. Associations between tumor-relevant biomarkers, genotypes and pCRs were evaluated using Student’s t-test for continuous variables and Chi-square or Fisher’s exact test for categorical variables. For univariate analysis, the relationship between the rs1042713 polymorphism and pCR was analyzed by Chi-square or Fisher’s exact test. The modified ORs with their 95% CIs were calculated by a multivariate logistic regression analysis to explore the association between genotype and pCR.ResultsThere was a significant correlation of the rs1042713 genotype with estrogen receptor (ER) status (P=0.008). Significant differences were detected in the rs1042713 genotypes of pCR and non-pCR patients (P=0.046). The pCR rate was 18.2% in patients with ADRB2 rs1042713 AA genotypes and 38.7% in AG+GG genotypes. Women carrying the AG+GG (OR=2.91, 95% CI: 1.02–8.29, P=0.046) genotype had a higher pCR rate than those with the AA genotype.Conclusionrs1042713, which is located in the ADRB2 gene, could predict pCR to taxane-and platinum-based neoadjuvant chemotherapy in LABC. This finding suggests that rs1042713 could play a potential role as a predictive marker in clinical settings.