Alpha-2b Research Articles

Ocular surface squamous neoplasia resistant to topical interferon alpha 2b in a patient with follicular lymphoma

Ocular surface squamous neoplasia resistant to topical interferon alpha 2b in a patient with follicular lymphoma

Association between the Trp64Arg polymorphism of the ADRB3 gene and overactive bladder.

The β3 -adrenergic receptor (ADRB3) is very important in the regulation of the human detrusor muscle function. The well-known tryptophan64arginine polymorphism of the ADRB3 gene alters the response of the receptor to various stimuli, including adrenalin and noradrenalin, and may increase the susceptibility to develop overactive bladder (OAB). Therefore, this study was performed to determine whether ADRB3 Trp64Arg polymorphism is associated with the pathophysiology of OAB syndrome. The study group (n = 150) consists of 72 patients with OAB and 78 controls without OAB. Venous blood samples were taken from all participants to analyze the ADRB3 gene Trp64Arg polymorphism using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay. We compared the distribution of Trp64Arg polymorphism and symptom severity in both OAB and non-OAB subjects using χ2 test and Mann-Whitney's U test, respectively. The frequency of the 64Arg variant (heterozygous plus homozygous) in OAB and non-OAB subjects was 15.3% and 14.1%, respectively. There was no statistically significant difference between the OAB and non-OAB groups in regard to the distribution frequency of ADRB3 Trp64Arg polymorphism. The total frequency (OAB + non-OAB, 76 women and 74 men) of the Arg64 variant allele was 5.9% and 10.8% in women and in men, respectively. Although the frequency of the Arg64 variant was nearly twofold higher in men compared to women, the difference was not statistically significant. These results demonstrated that the ADRB3 Trp64Arg polymorphism is not significantly associated with OAB syndrome in a sample of Turkish OAB patients.

Lower levels of tubulin alpha 1b in the frontal pole in schizophrenia supports a role for changed cytoskeletal dynamics in the aetiology of the disorder

Our transcriptomic study suggested there were markedly lower levels of tubulin alpha 1b (TUBA1B) expression in BA 10, but not BA 9, from patients with schizophrenia. We now use Western blotting to compare levels of TUBA1B protein in BA 9 and 10 from patients with schizophrenia and BA 10 from patients with mood disorders to controls as well as in the frontal cortex from rats after treatment with haloperidol, chlorpromazine or vehicle for 28 days. Levels of TUBA1B were significantly lower (- 18.6%) in BA 10, but not BA 9, from patients with schizophrenia. Levels of TUBA1B did not differ significantly from controls in BA 10 from patients with mood disorders or in the cortex of rats after antipsychotic drug treatments. Levels of TUBA1B were significantly lower (- 30%) in BA 10 from patients with schizophrenia who were not being treated with antipsychotic drugs close to death compared to those who were treated close to death. These data suggest that lower levels of TUBA1B, a cytoskeletal protein, in BA 10 from patients with schizophrenia are not a simple drug effect and therefore add to the hypothesis that a breakdown in cytoskeletal homoeostasis may be contributing to the genesis of the symptoms of the disorder.

Comparative Analysis of Adverse Drug Reactions between Interferon Alpha 2B and Sofosbuvir in the Treatment of Hepatits C at GIMHS, Sindh, Pakistan

A descriptive cross-sectional study was conducted on 300 patients selected by random sampling who were reported with Hepatitis-C at GIMHS. Questions were asked from patients regarding symptoms and adverse drug reactions (ADR’S). Results were analyzed by using SPSS-22. Out of total patients (n=300) the frequency of male gender was (n=192) as compared to females (n=108). Among 300 patients some patients were on sofosbuvir (n=150), patients on interferon (n=150). Rate of ADR’S observed with interferon as fever (n=28), anemia (n=27), hair loss (n=21), headache (n=19), insomnia (n= 11), nausea (n=13), depression (n=14, 09), malaise (n=25), vomiting (n=06), ulcer (n=13), pain and redness at site of injection (n=17). While rate of ADR’S in patients who were on sofosbuvir, fever (n=33), chill (n=17), nausea (n=28), anemia (n=06), headache (n=14), insomnia (n=13), loss of appetite (n=5), diarrhea (n=1). This study concluded that as compared to Interferon, rate of ADR’S were less with Sofosbuvir.

Association of ADRB2 gene polymorphism with dilated cardiomyopathy

Aim. To study the association of the rs1042713 polymorphism of the ADRB2 gene with cardiomyopathies of various origins.
 Material and methods. The study included patients with dilated cardiomyopathy (DCMP) and myocardial dilatation of ischemic genesis (DM IG).The total number of people surveyed is 221. The average age of the subjects was 55.309.69 years. Patients were divided into 2 groups: one of them patients with a diagnosis of dilated cardiomyopathy idiopathic (predictors of expansion of the heart cavities are excluded) and the other-patients with dilated myocardium of ischemic origin (a history of IHD). The number of patients in the first group was 111, including 99 (89.2%) men and 12 (10.8%) women. The average age of patients in this group is 51.739.74 years. The second group included patients with myocardial dilatation of ischemic origin. Their number is 110 people, including 100 (91.5%) men and 10 (8.5%) women. The average age of the respondents is 58.688.38 years. The control group consists of individuals who did not have any manifestations of cardiovascular diseases. Their number is 221 people (average age 53.64.8 years). Laboratory and instrumental studies, coronary angiography, and molecular genetic studies of the rs1042713 polymorphism of the ADRB2 gene were performed for all participants in the study. Those patients who were excluded predictors of the occurrence of dilation of the heart cavities were assigned to the first group. The second group included patients with a history of CHD.
 Results. In the group with DCMP, 10.8% of patients were carriers of the common homozygous AA genotype, the heterozygous AG genotype 48.6%, and the rare homozygous GG genotype 40.5%. In the group of patients with DM IG, 16.4% of patients were carriers of the common homozygous AA genotype, the heterozygous AG genotype 51.8%, and the rare homozygous GG genotype 31.8%. In the control group, 11.8% of patients were identified as carriers of the homozygous genotype for the common allele, 47.5% carriers of the heterozygous genotype, and 40.7% carriers of the homozygous genotype for the rare allele. No statistically significant results were obtained in the group of patients with DCMP and DM IG compared to the control group of the rs1042713 polymorphism of the ADRB2 gene.
 Conclusion. No association of ADRB2 gene rs1042713 polymorphism with DCMI and DM IG was revealed.

Ideas and methods of nonlinear mathematics and theoretical physics in DNA science: the McLaughlin-Scott equation and its application to study the DNA open state dynamics.

The online version contains supplementary material available at 10.1007/s12551-021-00801-0.

Genetic Determinants of Cardiovascular Reactions in Humans with Different Polymorphisms of the ADRB2 Gene in Response to the Diving Reflex

The diving reflex (DR) is a defense mechanism that evolved during adaptation to diving in secondary amniotes and humans. The adaptive cardiovascular response of the diving reflex is achieved through reflexive deceleration of the heart's rhythm, constriction of peripheral vessels (PVs) and selective redistribution of blood to those organs which are most vulnerable to hypoxia (the brain, heart, lungs). This is achieved by a complex interaction of cholinergic and adrenergic influences of higher and autonomous mechanisms of regulation of the heart and blood vessels. The aim of this study is to determine the dynamics of the reactions of the cardiovascular system during the implementation of the DR in subjects with different polymorphisms of the ADRB2 gene (p.Gly16Arg / rs1042713 / and p.Gln27Glu / rs1042714 /). 103 volunteers (students; aged 18-24) were examined. These subjects were not adapted to diving. DR was activated by submerging their faces in cold water (12-14◦C) under laboratory conditions. ECG records were taken for the resting state, during diving simulation and after apnea. The minute volume of blood flow (MVBF) was also determined for these states using rheography, and the blood supply to peripheral vessels was measured indirectly using the pulse wave amplitude (PWA) of the photoplethysmogram (PPG). Vascular tone was calculated from the time of its spread (the pulse transit time, PTT). Blood pressure was recorded. DNA samples from all patients’ blood were isolated using phenol-chloroform extraction. ADBR2 polymorphisms (p.Gly16Arg / rs1042713 / and p.Gln27Glu / rs1042714 /) were investigated using two-stage multiplex PCR followed by hybridization of alleles on a biochip. The results were analyzed using Mann-Whitney nonparametric tests (paired comparisons). On the whole, in the group of the subjects, during the implementation of the DR, a statistically significant decrease in heart rate, MVBF, PWA, indirectly reflecting the narrowing of peripheral vessels, as well as an increase in systolic and diastolic pressure is observed. No statistically significant change in stroke blood volume was found. In subjects with A/A (p.Gly16Arg) and C/C (p.Gln27Glu) polymorphisms of the ADRB2 gene during diving simulation, a statistically significant decrease in the PWA is observed, which indirectly reflects the tone of resistive peripheral vessels; In subjects with polymorphisms G/A (p.Gly16Arg) and C/G, G/G (p.Gln27Glu), no significant changes in this indicator were found during diving simulation. In subjects with polymorphisms with G/A and G/G (p.Gly16Arg) and C/C, G/C (p.Gln27Glu) of the ADRB2 gene, a statistically significant decrease in heart rate and a decrease in the MVBF were observed during diving simulation. Thus, not only the constrictor function of the vessels, but also the chronotropic function of the heart, reflexively realized in the test with diving simulation, significantly differs in those examined with different polymorphisms of the ADRB2 gene. The most pronounced constriction is observed in those examined with A/A p.Gly16Arg and C/C p.Gln27Glu, and slowing of heart rate in those examined with polymorphisms G/A and G/G p.Gly16Arg and C/C, G/C p.Gln27Glu of the ADRB2 gene.

Unpredictive Expression of recombinant proteins under the control of different promoters in different expression systems

Synthetic human proinsulin gene with E.coli preferred codon and extra methionine was expressed as 30% of total cellular protein. Fusing seven aminoacids of well expressed protein to the N’-terminus did not alter the expression of recombinant proinsulin. Doubling the copies of proinsulin gene will not doubles the expression. The protein was expressed as inclusion bodies. Changing the distances between ribosome binding site and start codon effect the expression in an unexplained way. Ten nucleotide distance gave expression of 2-4% and with 12 nucleotides, expression decreasaes up to 1-2%.. Incorporating 10 different nucleotides at the start of proinsulin gene decreases the mRNA secondary structure but did not alter the expression. Metabolic instability, rapid degradation of mRNA or accumulation of protein may down regulate expression of mRNA. High expression of azurin gene in pET22b vector was obtained when fused with 19 aminoacid signal peptide in BL21-Codon Plus (DE3) cells. PE38KDEL can be expressed in huge quantities in Escherichia coli by using the recombinant vector PE38KDEL/pET under control of T7 promoter and E. coli host strain BL21 (DE3) CodonPlus. The protein expressed as soluble and insoluble inclusion bodies the expression in soluble form was more pronounced. When human interferone alpha2|B gene and E.coli amino peptidase genes were expressed bicistronically in expression plasmid pET-21a (+). There was negligible expression of human interferone alpha 2B. PelB fused DNA polymerase I was expressed as soluble fraction with maximum expression with 0.5mM IPTG and 20mM lactose. Recombinant protein expression in expression host can be improved by mRNA stability, codon bias, and controlling inclusion bodies formation and changing genetic tools in different combinations. There are other controlling factors of protein expression i.e., metabolic instability, rapid degradation of mRNA or accumulation of protein may downregulate expression of mRNA.

Association of ADRB2 gene polymorphism with dilated cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University Aim To evaluate the Association of rs1042713 polymorphism of the ADRB2 gene with dilated idiopathic cardiomyopathy (DCMP) and myocardial dilation of ischemic origin (DMI). Subjects and methods The study included patients with ICMP and DMI in the number of 221 people. The average age of the subjects was in the range of 55.30 ± 9.69 years. We divided the patients into 2 groups: the first – patients diagnosed with idiopathic dilatation cardiomyopathy and the second-patients with myocardial dilatation of ichemic origin. The number of patients in the first group was 111, including 99 men (89.2%) and 12 women (10.8%). The average age of patients in this group is 51.73 ± 9.74 years, in men 51.00 ± 8.96 years, in women 57.75 ± 3.71 years. The second group included patients with myocardial dilatation of ischemic origin. Their number is 110 people, including 100 men (91.5%) and 10 women (8.5%). The average age of respondents is 58.68 ± 8.38 years, for men 58.29 ± 8.46 years, for women 62.90 ± 6.29 years. The control group included patients who had no manifestations of cardiovascular diseases. Their number is 121 people (average age 53.6 ± 4.8 years). The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the 16 AG polymorphism of the ADRB2 gene (rs1042713). All patients underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the first group. And those patients who were reliably diagnosed with CHD were in the second group, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. Results In the group with DCMP 10.8% of patients were carriers of the common homozygous 16AA genotype, the heterozygous 16AG genotype-48.6%, and the rare homozygous 16GG genotype-40.5%. In the control group 11.8% of patients were identified as carriers of a homozygous genotype by a common allele, and 47.5% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 40.7%. The analysis non revealed a statistically significant decrease in the frequency of carrying the homozygous 16GG genotype in patients with DCMP compared to the control group of the rs1042713 polymorphism of the ADRB2 gene. In the group with DM IG, there was no association with the rs1042713 polymorphism of the ADRB2 gene. Conclusion A statistically significant association of rs1042713 of the ADRB2 gene with DCMP was not found. The association of DMI c rs1042713 could not be confirmed.

Association of ADRB1 gene polymorphism with dilated cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University Aim To evaluate the Association of rs1801252 polymorphism of the ADRB1 gene with dilated idiopathic cardiomyopathy (DCMP) and myocardial dilation of ischemic origin (DMI). Subjects and methods The study included patients with ICMP and MD IG in the number of 221 people. The average age of the subjects was in the range of 55.30 ± 9.69 years. We divided the patients into 2 groups: the first – patients diagnosed with idiopathic dilatation cardiomyopathy and the second-patients with myocardial dilatation of ichemic origin. The number of patients in the first group was 111, including 99 men (89.2%) and 12 women (10.8%). The average age of patients in this group is 51.73 ± 9.74 years, in men 51.00 ± 8.96 years, in women 57.75 ± 3.71 years. The second group included patients with myocardial dilatation of ischemic origin. Their number is 110 people, including 100 men (91.5%) and 10 women (8.5%). The average age of respondents is 58.68 ± 8.38 years, for men 58.29 ± 8.46 years, for women 62.90 ± 6.29 years. The control group included patients who had no manifestations of cardiovascular diseases. Their number is 121 people (average age 53.6 ± 4.8 years). The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the A145G polymorphism of the ADRB1 gene (rs1801252 ). All patients underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the first group. And those patients who were reliably diagnosed with CHD were in the second group, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. Results In the group with DCMP 70.3% of patients were carriers of the common homozygous A145A genotype, the heterozygous A145G genotype-27.0%, and the rare homozygous G145G genotype-2.7%. In the control group 71.9% of patients were identified as carriers of a homozygous genotype by a common allele, and 25.3% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 2.7%. Statistical analysis showed no achievement of statistical significance level across any of the genotypes. In the group with DM IG, there was no association with the rs1801252 polymorphism of the ADRB1 gene. Conclusion A statistically significant association of rs1801252 of the ADRB1 gene with DCMP was not found. The association of DM IG c rs1801252 could not be confirmed.

АНАЛИЗ АССОЦИАЦИИ ПОЛИМОРФИЗМА ADRB2 ГЕНА И ФУНКЦИИ ВНЕШНЕГО ДЫХАНИЯ У ДЕТЕЙ С БРОНХИАЛЬНОЙ АСТМОЙ

Objectives. To study the role of the ADRB2 gene polymorphism (rs1042713) in the impaired external respiratory function in children with bronchial asthma (BA). Material and methods. The study group included 60 children aged 3-17 years with allergic (n=37) and mixed form of BA (n=23). The genotyping of the investigated gene locus was performed by PCR-RFLP (polymerase chain reaction - restriction fragment length polymorphism), BA control was exercised using the Asthma Control Test (ACT). Results. The analysis of allele frequencies showed an association of allele A with normal spirogram parameters in patients with BA (p=0.042). In children under 12 years, there were statistically significant differences in spirogram indices when comparing patients with genotypes AA and GG (p=0.045). An association of allele A with the absence of pathological changes was revealed when evaluating the results of spirometry (p=0.021). There was a moderate positive correlation (r=0.615, p=0.011) between the assessment of nocturnal symptoms (Asthma Control Test) and the genotype of the ADRB2 gene polymorphism in children aged 12 years and older. Conclusions. An association of the ADRΒ2 gene polymorphism (rs1042713) with the external respiratory function was revealed in an objective study by spirometry and a subjective assessment of this indicator by the patient himself/herself or by his/her parents. This gene locus can be included in the BA target panel in order to determine the likelihood of uncontrolled course development of the disease with impaired external respiratory function and in the future to develop an individual program for dispensary observation of the patient.

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.

Association of Beta-2 Adrenoreceptor Single Nucleotide Polymorphism with Risk of Type II Diabetes Mellitus

Objective: To determine the genotype of Arg16Gly & Gln27Glu polymorphism in type-2 diabetes mellitus and to find possible association of ADRβ2with type-2 diabetes mellitus. Methodology: A case control study was designed and a total of 192 subjects (98 in each group) were included. After formal approval, subjects were recruited from North West General Hospital (NWGH) Peshawar. After taking consent blood samples were collected from the participants and DNA analysis was done using commercially available kits by salting out protocols, while other biochemical parameters were analyzed using normal laboratory protocols for respective tests. Results: The comparative analysis of SNP rs1042713 indicates that allele G/A was 42(49.4%) in diabetic and 43(50.6%) in non-diabetic subjects. While GG was more frequent 22(59.5%) in diabetic as compare to non-diabetic 15(40.5%). Among AA allele, 19 (65.5%) were non-diabetic while 10(34.5%) were diabetic. However the difference was not statistically significant (p=0.22). In case of “rs1042714” gene the commonest allele was C/C 80 (41.7%) out of which, 47(58.8%) was found in diabetic and 33(41.2%) were non-diabetic. Similarly CG was second common allele out of which diabetics were 27(44.3%) while non-diabetics were 34(55.7%). Allele G/G was found only among 11 subjects (p=0.085). Conclusion: Based on the result of the present study, it is concluded that polymorphism in ADRB2 genes rs1042713 (Arg16Gly) and rs1042714 (Gln27Glu) is associated with susceptibility of T2DM through alteration in BMI & HbA1c.

Features of the COPD course in patients with different alleles of C79G (rs1072714) of ADRB2 gene

Chronic obstructive pulmonary disease (COPD) is a widely spread disease, that can be prevented and treated. As it was mentioned in the GOLD guidelines, genetic factors have a prominent impact on the development of COPD. A great amount of different genes is involved into the development of COPD. They influence processes of inflammation, fibrosis and regulation of airways reactivity. Polymorphism of ADRB2 gene is of a particular interest as it is associated with the development of COPD and response to beta-2 agonists, which are the main drugs used in the treatment of COPD. The aim of our study was to investigate an impact of the polymorphism of ADRB2 gene on the clinical course of COPD. We collected source data, medical history in all patients in order to assess smoking status and smoking experience, clinical group of COPD according to GOLD classification, total amount of exacerbations, exacerbations treated in in-patient and out-patient conditions, data about use of antibiotics, glucocorticosteroids and methylxanthines. Blood was collected in all patients for the genetic analysis of ADRB2 gene polymorphism. Among COPD patients 65 (65 %) had changes in ADRB2 gene. 26 patients (26 %) had mutation and 39 patients (39 %) had polymorphism of ADRB2 gene, which indicate possible relation of ADRB2 gene with the COPD development. Patients of group 1, C79C allele carriers, had milder COPD course, which presented with the significant difference in the of GOLD D patients in this group (17.14±7.13 %) and group 2, C79G allele carriers, (58.97±8.15 %) and group 3, G79G allele carriers, (34.61±9.59 %). Group 1 patients had lower amount of exacerbations (2.543±0.281) when compared to group 3 (2.963±0.273), and lower amount of hospital admissions (1.031±0.154) when compared to group 2 (1.332±0.167). Group 1 patients also used less antibiotics then other groups. So, ADRB2 gene polymorphism in C79G positions is a prognostic factor of the severity of COPD course. It is associated with the greater amount of exacerbations and hospitalizations and also greater antibiotic use.

Association of beta-adrenergic reactivity index of erythrocyte membranes in myocardial infarction with genetic features of the beta-adrenoreceptor apparatus

Objective: To study the association of beta-adrenergic reactivity index of erythrocyte membranes with polymorphisms of the beta-1-adrenergic receptor gene ADRB1 (Ser49Gly and Arg389Gly).Material and methods: the study included 62 patients with myocardial infarction (MI) — 49 men (median age of 58.0 (47.5; 64.5) years) and 13 women (median age of 76.0 (61.5; 81.0) years). All patients underwent analysis of beta-adrenoreactivity of erythrocyte membranes using the BETA-ARM AGAT reagent kit within the first 6 hours from the onset of MI. The patients were divided into 2 groups depending on the value of the beta-adrenergic reactivity index (β-ARM). The first group (n = 11) included patients with a normal P-ARM level (from 2 to 20 conventional units). The second group (n = 51) consisted of patients with increased values of β-ARM (more than 20 standard units). Genetic analysis for the determination of ADRB1 gene polymorphisms (Ser49Gly and Arg389Gly) was carried out by isolating DNA from peripheral blood leukocytes (Wizard Genomic DNA Purification Kit) with PCR amplification and further electrophoretic detection. Statistical processing of the obtained data was carried out using Statistica 10 software and the demo version of IBM SPSS Statistics 20.0.Results: patients with elevated β-APM values were characterized by higher levels of myocardial necrosis markers in the blood (CPK, CPK-MB, and troponin I) in acute myocardial infarction than for patients of the first group (p = 0.009, p = 0.032 and p = 0.001, respectively). In addition, the second group of patients was characterized by a more frequent development of acute left ventricular failure (33.3%, p = 0.026), as well as a history of arterial hypertension before the development of index MI (90.2%, p = 0.044). With regard to the Arg389Gly polymorphism, significant differences were found among patients with normal and increased P-APM values in the acute period of MI. Thus, the second group of patients consisted mainly of carriers of the 1165CC genotype of the ADRB1 gene (n = 29, 56.9%, p = 0.043). The carriage of the 1165G allele was much more often observed among patients of the first group (81.8%; OR = 5.93; CI 1.16-30.25; p = 0.043).Conclusion: an association of the 1165CC genotype of the Arg389Gly polymorphism of the ADRB1 gene with increased β-APM values in acute MI was established. The detected associations may indicate a possible genetic predisposition to SAS hyperactivation, and also indicate the need for further study of polymorphisms and the level of expression of the ADRB1 gene in patients with high individual values of β-APM established in the acute period of MI.

Identify potential miRNA-mRNA regulatory networks contributing to high-risk neuroblastoma.

Neuroblastoma (NB) is a common tumor in children, usually in the retroperitoneum. After various treatments, low- and intermediate-risk patients have achieved good results, but the prognosis of high-risk patients is still very poor. Therefore, it is necessary to find new effective targets for the treatment of high-risk patients. In this study, comprehensive bioinformatics analysis was used to identify the differentially expressed genes (DEG and DEM) between high-risk patients and non-high-risk patients, and it was identified that ADRB2 may affect the survival status of high-risk patients due to miR -30a-5p regulation. The GSE49710, GSE73517, and GSE121513 datasets were downloaded from the Gene Expression Synthesis (GEO) database, and DEG and DEM were selected. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied to the selected DEGs. The STRING database and Cytoscape software were used to construct protein-protein interaction (PPI) networks and perform modular analysis of the DEGs. The TARGET data set containing information on overall survival days were used for the prognostic analysis of central genes. We identified a total of 255 DEGs from GSE49710 and GSE73517, and 193 DEMs from GSE121513. We identified the 5 most important central genes from the PPI network, performed a prognostic analysis in the target data set, and verified their expression using RT-qPCR to select the most important ADRB2 gene to predict miRNA. Integrating the differential miRNA predicted by miRDB and miRSystem and GSE121513 between the targeted miRNA and the prognosis, miR-30a-5p was finally identified as the targeted miRNA of ADRB2.

The role of ADRB2 gene polymorphisms in malignancies.

Beta-2-adrenergic receptor is a member of the G protein-coupled receptor superfamily, which is highly expressed in most malignancies. There is increasing evidence showing that beta-2-adrenergic receptors are associated with carcinogenesis, proliferation, immune regulation, invasion, angiogenesis, clinical prognosis and treatment resistance in malignancies. Polymorphisms of the ADRB2 gene have been confirmed to be associated with transcriptional activity, mRNA translation, and beta-2-adrenergic receptor expression and sensitivity. This review discusses clinically relevant examples of single nucleotide polymorphisms of ADRB2 in malignancies and the effects of these polymorphisms on cancer susceptibility, prognosis and treatment response of cancer patients.

Mutational landscape and potential therapeutic targets for sporadic pancreatic neuroendocrine tumors based on target next-generation sequencing.

Pancreatic neuroendocrine tumor (PNET), a heterogenous type of neoplasm with limited treatment options, is relatively rare and to date, the genetic background has remained to be fully elucidated. The present study aimed to determine the mutational landscape of PNET with and without liver metastasis, as well as its clinical application value for treatment. Fresh tumor tissues were collected from 14 patients with PNET following surgery, 4 of whom had developed liver metastasis. Subsequently, targeted next-generation sequencing of 612 cancer-associated genes and comprehensive analysis were performed on the tumor tissues. The results identified 63 somatic mutations in 53 genes in the 14 patients with PNET, amongst which menin 1 was identified as the most recurrently mutated gene. The analysis also identified several novel recurrently mutated genes, including adrenoceptor alpha 2B, ARVCF delta catenin family member, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase and neuregulin 1. Among the 53 mutated genes, 11 were enriched in the PI3K/AKT signaling pathway (adjusted P=7.12x10-5). In addition, 4 patients with PNET with liver metastasis had distinctly different mutational profiles compared with those without liver metastasis; 13 genes were discovered to be exclusively mutated in the liver metastasis group of the patients with PNET, including ATRX chromatin remodeler, thioredoxin reductase 2, anus kinase 3, ARVCF delta catenin family member, integrin subunit alpha V and RAD50 double strand break repair protein. In addition, two potentially actionable alterations in BRCA2 DNA repair-associated (p.Q548Q) and neurofibromin 1 (p.Q1188X) were identified using the OncoKB database. In conclusion, the present study generated a comprehensive mutational profile of 14 patients with PNET and further described the features of patients with liver metastasis, which highlights potential targets for drug development of PNET.

Abdominal pain in patients with inflammatory bowel disease: association with single-nucleotide polymorphisms prevalent in irritable bowel syndrome and clinical management

BackgroundAbdominal pain is a frequent symptom in patients with inflammatory bowel disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC). Pain can result from ongoing inflammation or functional disorders imitating irritable bowel syndrome (IBS). Several single-nucleotide polymorphisms (SNPs) have been associated with IBS. However, the impact of IBS genetics on the clinical course of IBD, especially pain levels of patients remains unclear.MethodsData of 857 UC and 1206 CD patients from the Swiss IBD Cohort Study were analysed. We tested the association of the maximum of the abdominal pain item of disease activity indices in UC and CD over the study period with 16 IBS-associated SNPs, using multivariate ANOVA models.ResultsIn UC patients, the SNPs rs1042713 (located on the ADRB2 gene) and rs4663866 (close to the HES6 gene) were associated with higher abdominal pain levels (P = 0.044; P = 0.037, respectively). Abdominal pain was not associated with any markers of patient management in a model adjusted for confounders. In CD patients, higher levels of abdominal pain correlated with the number of physician contacts (P < 10–15), examinations (P < 10–12), medical therapies (P = 0.023) and weeks of hospitalisation (P = 0.0013) in a multivariate model.ConclusionsWe detected an association between maximal abdominal pain in UC patients and two IBS-associated SNPs. Abdominal pain levels had a pronounced impact on diagnostic and therapeutic procedures in CD but not in UC patients.

Safety, Immune, and Antiviral Effects of Pegylated Interferon Alpha 2b Administration in Antiretroviral Therapy-Suppressed Individuals: Results of Pilot Clinical Trial

In the pilot NCT01935089 trial, we tested whether pegylated interferon alpha2b (Peg-IFN-α2b) with antiretroviral therapy (ART) was safe and could impact HIV and immune measures in blood and in gut-associated lymphoid tissue (GALT). Twenty HIV-1+ ART-suppressed individuals received 1 μg/kg/week Peg-IFN-α2b with ART for 20 weeks, with intermediate 4-week analytical ART interruption (ATI). Safety, immune activation, HIV viral load and integrated HIV DNA in blood, and HIV RNA and DNA in gut biopsies were measured. A total of 7/20 participants experienced grade 3-4 adverse events, while 17/20 participants completed the study. Of the 17 participants who completed the study, 8 remained suppressed during ATI, while all 17 were suppressed at end of treatment (EoT). As expected, treatment increased activation of T and natural killer (NK) cells and IFN-stimulated molecule expression on monocytes in periphery. While circulating CD4+ T cells showed a trend for a decrease in integrated HIV DNA, GALT showed a significant decrease in HIV-1 RNA+ cells as measured by in situ hybridization along with a reduction in total HIV DNA and cell-associated RNA by EoT. The observed decrease in HIV-1 RNA+ cells in GALT was positively associated with the decrease in activated NK cells and macrophages. This study documents for the first time that 20 weeks of immunotherapy with Peg-IFN-α2b+ART (inclusive of a 4-week ATI) is safe and results in an increase in blood and GALT immune activation and in a significant decrease in HIV-1 RNA+ cells in GALT in association with changes in innate cell activation.