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.

Association study of the beta-adrenergic receptor genetic variant Gly389Arg and fluoxetine response in major depression

Background: Pharmacogenetics has proven role in the treatment of different illnesses. Patients with special genotypes may achieve a better response to a specific drug. On the other hand, genetic parameters markedly contribute to the development of major depressive disorder (MDD). The significance of adrenergic system compartments in cognition and behavior, and their role in etiology of depression denote that adrenergic receptors beta gene polymorphism(s) might also have an association with drug response. Thus this study aims to evaluate the association between β1AR gene polymorphisms, G1165C, Arg389Gly and response to fluoxetine in MDD patients. Materials and Methods: Among different antidepressants, we focused on fluoxetine as it is prescribed frequently in MDD and belongs to one of the most efficient antidepressant categories with minimum side effects. MDD was diagnosed at study entry using DSM-IV criteria. One hundred and one new MDD patients were treated with fluoxetine for a period of 6 weeks. A 50% decrease in Hamilton Rating Scale for Depression (HRSD) was considered as response to treatment. Genotyping of G1165C polymorphism was performed by PCR-RFLP method. Results: Results of the study indicated no significant relationship between β1AR polymorphism and the patient’s response to fluoxetine neither at genotypic nor allelic level (P=0.568). Conclusion: Our study did not support the hypothesis of involvement of β1AR Arg389Gly polymorphism and response to fluoxetine in MDD patients. [GMJ.2020;9:e1781]

The bisoprolol efficiency predictors in patients with stable angina after myocardial infarction

Objective: to identify the of bisoprolol effectiveness predictors in patients with stable angina after myocardial infarction.Materials and methods: 107 patients with stable angina who underwent myocardial infarction aged 35–65 years (mean age 54,7 ± 6,2 years) were examined in an open, comparative, register study, of which groups were generated: with the achieved and unreached target heart rate (60 or less in 1 minute). Additionally, the respondents were stratified into subsamples by the presence of ADRB1 gene Arg389Gly polymorphism. All patients underwent a 5-minute study of heart rate variability (HRV) in the background sample and in active orthostasis and the determination of the ADRB1 gene polymorphism (Arg389Gly, rs1801253) by PCR. All patients received bisoprolol in the selected optimal maximum-tolerated dose.The main results: respondents who did not reach the target heart rate significantly more often complained about heartbeat and heart rhythm interruptions (p = 0,003), increased incidence of cardiac pain episodes (p = 0,02), noted a high demand for nitrates (p = 0,03) and significantly more often sought medical help. In respondents with the achieved target heart rate, sympathetic influences were less expressed in the background HRV sample with significantly higher parasympathetic influences expression by contrast. The number of sympathicotonics in terms of HRV at rest was significantly higher among respondents with unreached heart rate. When comparing the frequencies of alleles in respondents with the achieved target heart rate, a significant (p = 0.0001) prevalence of carriers of the Gly allele of the ADRB1 gene Arg389Gly polymorphism was revealed. The heart rate in carriers of the Gly allele in homo-or heterozygous form was significantly lower than in carriers of the homozygous genotype Arg389Arg.Conclusion: The predictors of the bisoprolol effectiveness in achieving the target heart rate in patients with stable angina after MI are: a stress index less than 104.5 cu. in the background sample of a 5-minute HRV, the presence of the polymorphic Gly allele of the ADRB1 gene Arg389Gly polymorphism, the age of less than 46 years, and the total spectrum power in the background HRV sample of more than 1309 ms.

Abstract 39: Frequency of the Angiotensin Converting Enzyme (I/D) and β1 Adrenergic Receptor (Arg389Gly) Gene Polymorphisms in a Sample of Mexican Population

Introduction: The angiotensin converting enzyme (ACE) is involved in blood pressure regulation. The I/D polymorphism of ACE has been associated with hypertension, left ventricular hypertrophy and metabolic syndrome. The β1 adrenergic receptor (ARβ1) is located mainly in the heart, its activation has a chronotropic and inotropic effect. The Arg389Gly polymorphism of ARβ1 has been associated with dilated cardiomyopathy, atrial fibrillation and vasovagal syncope. The identification of these polymorphisms in a control group, will reveal the frequencies in healthy mexican population so we can compare with the diseased population and seek association with different diseases. Objective: Identifying gene and allelic prevalence in a healthy population. Material and Methods: We worked with 45 samples from healthy individuals, 36 males and 9 females, with a median age of 35.8 ± 16.1 and a BMI of 25.81 ± 4.6. Extraction of DNA from 10 ml of peripheral blood. ACE polymorphism was determined by direct PCR. The determination of the Arg389Gly polymorphism was by PCR-RFLP. Results: The gene frequency of the ACE gene in 39 subjects was: DD 33.33% (13 of 39), ID 38.46% (15 of 39) and II 28.2% (11 of 39). The allelic frequency: I 47.43% and D 52.56%. Arg389Gly polymorphism frequency was in 11 subjects: ArgArg 9% (1 of 11), ArgGly 72.7% (8 of 11) and GlyGly 18.2% (2 of 11). The allele frequency: 45% Arg and Gly 55%. Conclusions: DD homozygote frequency differs from that observed in the study of Vargas et al., which is lower. This is important because the D allele is associated with greater activity and concentration of ACE, which may predispose to cardiovascular disease in our population. Regarding the Arg389Gly polymorphism, it has been observed that the Gly allele is linked to cardiovascular disease and the response to beta-blockers. Our population showed an increase of Gly allele carriers, so they may be more susceptible to these diseases. It is important to know the frequency of these polymorphisms in our population, and identify that they can impact in medical treatment or may serve as potential predictors of cardiovascular disease.