Associative studies of polymorphic variants of adrenergic receptor genes and tardive dyskinesia in schizophrenia

2021 ◽  
pp. 36-40
Author(s):  
И.В. Пожидаев ◽  
Д.З. Падерина ◽  
О.Ю. Федоренко ◽  
А.С. Бойко ◽  
Е.Г. Корнетова ◽  
...  
Keyword(s):  
Tardive Dyskinesia ◽  
Adrenergic Receptor ◽  
Polymorphic Variant ◽  
Adrenergic System ◽  
Antipsychotic Therapy ◽  
Schizophrenic Patients ◽  
Basic Functions ◽  
Polymorphic Variants ◽  
First Time

Адренергическая система, наряду с дофаминергической, серотонинергической и глутаматергической системами, играет важную роль в патофизиологии шизофрении и ответе на применяемую фармакотерапию. Тардивная или поздняя дискинезия (ТД) относится к серьезным побочным эффектам и может развиваться у больных шизофренией на фоне длительного использования антипсихотиков. Важная роль в патогенезе ТД принадлежит генетическим факторам. Целью настоящего исследования явился поиск возможных ассоциаций полиморфных вариантов генов ADRβ1 и ADRA1A с развитием ТД у больных шизофренией, получающих антипсихотическую терапию. Выборка составила 449 пациентов из русской популяции Сибирского региона с верифицированным диагнозом шизофрения, из которых 121 пациент соответствовал критериям ТД. Генотипирование полиморфных вариантов rs1801253, rs2036108, rs472865 генов ADRβ1 и ADRA1A проведено методом ПЦР в реальном времени амплификатором QuantStudio 5 с использованием наборов TaqMan. Ассоциативный анализ частот генотипов и аллелей оценивался с помощью критерия χ2 в программе R 3.6.2 с использованием базовых функций и дополнительного пакета SNPassoc. Распределение частот генотипов и аллелей для полиморфного варианта rs2036108 гена ADRA1A значимо отличается в группах пациентов с ТД и без побочного эффекта (для генотипов р = 0,028; для аллелей р = 0,040). Впервые была выявлена ассоциация полиморфного варианта rs2036108 гена ADRA1A с ТД у больных шизофренией. Необходимы дальнейшие исследования роли генов адренергических рецепторов в развитии ТД для разработки фармакогенетических подходов к персонализации терапии. The adrenergic system, along with the dopaminergic, serotonergic and glutamatergic systems, plays an important role in the pathophysiology of schizophrenia and response to the applied pharmacotherapy. Tardive or late dyskinesia (TD) is a serious side effect and can develop in schizophrenic patients with prolonged use of antipsychotics. An important role in the pathogenesis of TD belongs to genetic factors. The aim of this study was to search for possible associations of polymorphic variants of the ADRβ1 and ADRA1A genes with the development of tardive dyskinesia in schizophrenic patients receiving antipsychotic therapy. We examined 449 patients from Russian population of Siberian region with verified diagnosis of schizophrenia. 121 patients from whole group met the criteria for tardive dyskinesia. Genotyping of the polymorphic variants rs1801253, rs2036108, rs472865 of the ADRβ1 and ADRA1A genes was performed by real-time PCR using a QuantStudio 5 amplifier using TaqMan kits. The associative analysis of the frequencies of genotypes and alleles was assessed using the χ2 test in the R 3.6.2 program using basic functions and an additional SNPassoc package. The distribution of genotype and allele frequencies for the rs2036108 polymorphic variant of the ADRA1A gene significantly differs in the groups of patients with tardive dyskinesia and without side effects (for genotypes p = 0.028; for alleles p = 0.040). For the first time, the association of the rs2036108 polymorphic variant of the ADRA1A gene with tardive dyskinesia in schizophrenic patients was revealed. Further studies of the role of adrenergic receptor genes in the development of tardive dyskinesia are required to develop pharmacogenetic approaches to personalizing therapy.

beta-Receptor influence on lung vasoconstrictor responses to hypoxia and humoral agents

1977 ◽  
Vol 43 (4) ◽  
pp. 612-616 ◽  
Author(s):  
R. J. Porcelli ◽  
A. T. Viau ◽  
N. E. Naftchi ◽  
E. H. Bergofsky
Keyword(s):  
Adrenergic Receptor ◽  
Adrenergic System ◽  
Hypercapnic Acidosis ◽  
Pulmonary Tissue ◽  
Beta Adrenergic ◽  
Vascular Responses ◽  
Adenosine Cyclic Monophosphate ◽  
Adrenergic Activity ◽  
Camp Levels

The role of the adrenergic receptor in mediating pulmonary vascular responses to gaseous and humoral agents was investigated by use of epinephrine injections in the perfused feline pulmonary circulation. Alteration of the balance between alpha- and beta-adrenergic activity was quantified by measurement of decreasing vasoconstrictor activity to epinephrine and rising lobar tissue 3′,5′-adenosine cyclic monophosphate (cAMP) levels. The increased beta-adrenergic activity thus generated was associated with marked reductions in the pulmonary vasoconstrictor responses to hypoxia, hypercapnic acidosis, and histamine, but not to serotonin. Repeated pulmonary vasodilations or increases in blood, but not pulmonary tissue, levels of cAMP induced by theophylline doses, which would not necessarily affect the beta-adrenergic activity, did not alter the pulmonary vasoconstrictor responses to hypoxia, hypercapnia, or histamine. These data support the significant role which the adrenergic system plays in mediating pulmonary vasoconstrictor responses to certain specific gaseous and humoral agents, and the specificity with which this mediation occurs serves to link hypoxia and histamine together so that the latter could serve as a mediator of the former.

Late Onset Involuntary Movements in Chronic Schizophrenia: Relationship of ‘Tardive’ Dyskinesia to Intellectual Impairment and Negative Symptoms

1986 ◽  
Vol 149 (5) ◽  
pp. 616-620 ◽  
Author(s):  
J. L. Waddington ◽  
H. A. Youssef
Keyword(s):  
Tardive Dyskinesia ◽  
Negative Symptoms ◽  
Late Onset ◽  
Chronic Schizophrenia ◽  
Intellectual Impairment ◽  
Medication History ◽  
Involuntary Movements ◽  
Schizophrenic Patients ◽  
Relationship Of

Intellectual impairment, negative symptoms, and medication history were assessed in chronic schizophrenic patients with and without abnormal involuntary movements (tardive dyskinesia). Patients with involuntary movements had received neither longer nor more intensive treatment with neuroleptics or anticholinergics. However, the presence or absence of involuntary movements was prominently associated with the presence or absence of intellectual impairment/negative symptoms; these features are characteristic of the defect state/type II syndrome of schizophrenia, in which structural abnormalities of the brain may be over-represented. The role of subtle organic changes in conferring vulnerability to the emergence of such involuntary movements should be re-evaluated.

scholarly journals β-Adrenergic receptor stimulation inhibits proarrhythmic alternans in postinfarction border zone cardiomyocytes: a computational analysis

2017 ◽  
Vol 313 (2) ◽  
pp. H338-H353 ◽  
Author(s):  
Jakub Tomek ◽  
Blanca Rodriguez ◽  
Gil Bub ◽  
Jordi Heijman
Keyword(s):  
Adrenergic Receptor ◽  
Border Zone ◽  
Adrenergic Stimulation ◽  
Cell Coupling ◽  
Postmyocardial Infarction ◽  
Model Cell ◽  
Cycle Lengths ◽  
Underlying Mechanisms ◽  
First Time

The border zone (BZ) of the viable myocardium adjacent to an infarct undergoes extensive autonomic and electrical remodeling and is prone to repolarization alternans-induced cardiac arrhythmias. BZ remodeling processes may promote or inhibit Ca2+ and/or repolarization alternans and may differentially affect ventricular arrhythmogenesis. Here, we used a detailed computational model of the canine ventricular cardiomyocyte to study the determinants of alternans in the BZ and their regulation by β-adrenergic receptor (β-AR) stimulation. The BZ model developed Ca2+ transient alternans at slower pacing cycle lengths than the control model, suggesting that the BZ may promote spatially heterogeneous alternans formation in an infarcted heart. β-AR stimulation abolished alternans. By evaluating all combinations of downstream β-AR stimulation targets, we identified both direct (via ryanodine receptor channels) and indirect [via sarcoplasmic reticulum (SR) Ca2+ load] modulation of SR Ca2+ release as critical determinants of Ca2+ transient alternans. These findings were confirmed in a human ventricular cardiomyocyte model. Cell-to-cell coupling indirectly modulated the likelihood of alternans by affecting the action potential upstroke, reducing the trigger for SR Ca2+ release in one-dimensional strand simulations. However, β-AR stimulation inhibited alternans in both single and multicellular simulations. Taken together, these data highlight a potential antiarrhythmic role of sympathetic hyperinnervation in the BZ by reducing the likelihood of alternans and provide new insights into the underlying mechanisms controlling Ca2+ transient and repolarization alternans. NEW & NOTEWORTHY We integrated, for the first time, postmyocardial infarction electrical and autonomic remodeling in a detailed, validated computer model of β-adrenergic stimulation in ventricular cardiomyocytes. Here, we show that β-adrenergic stimulation inhibits alternans and provide novel insights into underlying mechanisms, adding to a recent controversy about pro-/antiarrhythmic effects of postmyocardial infarction hyperinnervation. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/%CE%B2-ar-stimulation-and-alternans-in-border-zone-cardiomyocytes/ .

RESEARCH ON POLYMORPHIC VARIANTS CANDIDATE GENES FOR PSORIASIS

Vestnik ◽  
2021 ◽  
pp. 202-207
Author(s):  
К. Д. Ковалёва ◽  
Г.С. Бисмилдина ◽  
А. Толегенкызы ◽  
З.С. Качиева
Keyword(s):  
Gene Polymorphism ◽  
Human Genome ◽  
Candidate Genes ◽  
Polymorphic Variant ◽  
International Database ◽  
Ensembl Database ◽  
Genotype Frequencies ◽  
Polymorphic Variants ◽  
First Time ◽  
Pou5f1 Gene

В статье рассмотрены результаты исследования полиморфных вариантов генов предрасположенности к псориазу PSORS1C1, POU5F1, IL23R. Исследованы 192 образца ДНК, из них 116 образцов (77 больных псориазом и 39 человек, без признаков данной патологии) соответствовали стандартным требованиям к пробам ДНК. Полученные результаты сравнивались с референсной версией генома человека CRch 37. Распределение частот генотипов полиморфных вариантов трех генов соответствовали уравнению Харди-Вайнберга. Установлены 17 полиморфных вариантов локуса PSORS1C1, один вариант полиморфизма гена POU5F1 и два варианта полиморфизма гена IL23R, представленных в международной базе данных Ensembl. Впервые, выявлен еще один полиморфный вариант гена IL23R, ранее не аннотированный в базе данных Ensembl. The article discusses the results of the study of polymorphic variants of the PSORS1C1, POU5F1, IL23R genes which predisposition to psoriasis. 192 DNA samples were examined, in which 116 samples (77 patients with psoriasis and 39 people without signs of this pathology) met the standard requirements for DNA samples. Obtained results were compared with the reference version of the human genome CRch 37. The distribution of the genotype frequencies of the polymorphic variants of the three genes corresponded to the Hardy-Weinberg equation. Identified 17 polymorphic variants of the PSORS1C1 locus, one variant of the POU5F1 gene polymorphism and two variants of the IL23R gene polymorphism, which presented in the international database Ensembl. For the first time, identified another polymorphic variant of the IL23R gene, which had not been previously annotated in the Ensembl database.

scholarly journals The role of gene regulatory sites in development predisposition to preeclampsia

2020 ◽  
pp. 35-38
Author(s):  
В.Н. Сереброва ◽  
Е.А. Трифонова ◽  
А.Ю. Ворожищева ◽  
В.А. Степанов
Keyword(s):  
Ethnic Groups ◽  
Genetic Architecture ◽  
Placental Tissue ◽  
Regulatory Mechanisms ◽  
Expression Variability ◽  
Polymorphic Variants ◽  
Gene Regulatory ◽  
First Time ◽  
Regulatory Sites

Преэклампсия (ПЭ) - одно из наиболее тяжелых гипертензивных расстройств беременности, этиология и патогенез которого оста- ются на сегодняшний день плохо изученными. Поскольку ключевая роль в этиопатогенезе ПЭ отводится плацентарной ткани, изу- чение вариабельности уровня экспрессии генов в плаценте и механизмов регуляции данных изменений являются перспективными направлениями. Цель исследования - охарактеризовать генетическую архитектуру ПЭ по системе регуляторных однонуклеотидных полиморфизмов (rSNP) нового гена-кандидата SYDE1 , выявленного впервые по результатам анализа транскриптома плацентарной ткани. В работе было изучено два наиболее значимых rSNP гена SYDE1 (rs56153523, rs8109071). Исследование проводилось в трех этнических группах: буряты, русские, якуты. Результаты проведенного исследования демонстрируют ассоциацию rSNP гена SYDE1 с развитием ПЭ в выборках бурятов (rs56153523) и русских (rs56153523, rs8109071). Preeclampsia (PE) is one of the most serious hypertensive pregnancy disorders, which etiology and pathogenesis is remained poorly under- stood. Since a key role in the etiopathogenesis of PE is given to the placental tissue, the study of the gene expression variability in the pla- cental tissue and of the regulatory mechanisms of these changes is a promising approach. The purpose of this research was to characterize of the genetic architecture of PE on the basis of regulatory polymorphic variants (rSNPs) of the new SYDE1 candidate gene, identified for the first time by the results of the transcriptome analysis in placental tissue. In this work, we analyzed the two most significant rSNPs of the SYDE1 gene (rs56153523, rs8109071). The study was conducted in three ethnic groups: Buryats, Russians, Yakuts. We have detected associations of the rSNPs of SYDE1 gene with the development of preeclampsia in ethnic groups Buryat (rs56153523) and Russian (rs56153523, rs8109071).

Role of angiotensin II, alpha-adrenergic system, and arginine vasopressin on arterial pressure in rat

1984 ◽  
Vol 246 (1) ◽  
pp. H25-H30 ◽  
Author(s):  
M. S. Paller ◽  
S. L. Linas
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Arginine Vasopressin ◽  
Adrenergic Receptor ◽  
Enzyme Inhibitor ◽  
Adrenergic System ◽  
Ang Ii ◽  
Conscious Rat ◽  
Profound Hypotension

Three pressor systems regulate arterial pressure (MAP): angiotensin II (ANG II), the alpha-adrenergic system, and arginine vasopressin (AVP). In this study we determined the ability of each system to support MAP in the conscious rat when the other two systems were inactivated. After administration of the converting-enzyme inhibitor teprotide (CEI) and the alpha-adrenergic receptor antagonist phenoxybenzamine (POB), MAP decreased 40% as a result of a 45% decrease in peripheral vascular resistance (PVR). Despite hypotension, plasma AVP levels were not increased, and an AVP pressor antagonist (AVP-A) did not result in a further decrease in MAP. Thus the profound hypotension after POB plus CEI was the result of inhibition of all three systems. POB, rather than CEI, prevented AVP release since following hypotensive hemorrhage, plasma levels reached 51 +/- 13 pg/ml with CEI but only 4.7 +/- 0.8 pg/ml with POB. To study the pressor effect of AVP alone, AVP was infused in POB plus CEI-treated rats. AVP increased MAP (from 68 +/- 4 to 92 +/- 5 mmHg; P less than 0.005) and plasma AVP (to 13.8 +/- 1.9 pg/ml). Since POB inhibited both the AVP and the alpha-adrenergic system, the role of ANG II alone was determined in POB-treated rats. In the presence of ANG II MAP was 97 +/- 1 mmHg. To study the alpha-adrenergic system, MAP was determined in CEI plus AVP-A-treated rats. In the presence of an intact alpha-adrenergic system MAP was 101 +/- 1 mmHg. We conclude that PVR and MAP are profoundly decreased in the absence of all three pressor systems.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of the hypothalamic β-adrenergic system in controlling the LH rise in short-term castrated rats

1987 ◽  
Vol 114 (2) ◽  
pp. 167-172 ◽  
Author(s):  
M. H. Al-Hamood ◽  
D. P. Gilmore ◽  
C. A. Wilson ◽  
P. Tuohy-Jones ◽  
S. Drummond ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Concomitant Administration ◽  
Inhibitory Effect ◽  
Adrenergic System ◽  
Receptor Subtypes ◽  
Short Term ◽  
Pharmacological Agents ◽  
Inhibitory Component ◽  
Lh Release

ABSTRACT Intraventricular infusions of adrenaline and various pharmacological agents acting on β-adrenergic receptor subtypes were carried out in rats orchidectomized 16 h previously. Infusions (10 μl) of solutions containing the drugs were administered under anaesthesia induced with alphaxalone and alphadolone. Levels of LH were measured in plasma collected immediately before and at predetermined intervals after the infusion. The acute rise in LH levels after castration was increased still further by isoprenaline (a mixed β1- and β2-agonist), fenoterol (a β2-agonist) and atenolol (a β1-antagonist). In contrast, prenalterol (a β1-agonist) and (2RS,3RS)-3-isopropylamino-1-(7-methylindan-4-yloxy)butan-2-ol (ICI 118 551) (a selective β2-antagonist) were inhibitory to LH release. Adrenaline itself, salbutamol (another selective β2-agonist), propranolol (a mixed β-antagonist) and metoprolol (a β1-antagonist) did not significantly alter plasma LH concentrations at the doses administered. The stimulatory effect of isoprenaline on LH release was partially reduced when given together with ICI 118 551, but was not affected when administered simultaneously with atenolol. The inhibitory effect of ICI 118 551 was, however, prevented by concomitant administration with fenoterol, as was that of prenalterol when infused with atenolol. The results suggest that the hypothalamic mediation of the short-term changes in LH release in response to castration is exerted, at least in part, through the activation of a β2-stimulatory component and the suppression of a β1-inhibitory component. J. Endocr. (1987) 114, 167–172

scholarly journals Polymorphic variants of xenobiotic metabolism genes and body mass index in schizophrenia patients receiving antipsychotic therapy

2019 ◽  
pp. 115-117
Author(s):  
I. V. Pozhidaev ◽  
A. S. Boiko ◽  
E. G. Kornetova
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Side Effect ◽  
Metabolic Disorders ◽  
Antipsychotic Drugs ◽  
Common Side Effect ◽  
Siberian Region ◽  
Antipsychotic Therapy ◽  
Schizophrenic Patients ◽  
Polymorphic Variants

The use of atypical antipsychotic drugs has made metabolic disorders one of the most common side effect of pharmacotherapy for schizophrenic patients. The aim of this study was to assess the contribution of polymorphic variants of genes of the P450 cytochrome system to changes in body mass index in patients with schizophrenia. As a result of the study, we did not identify significant associations of genotypes and alleles of the studied polymorphic variants of the CYP2D6, CYP1A2, CYP2C19 genes with weight gain in patients with schizophrenia of Russian nationality of the Siberian region receiving antipsychotic therapy and can revealed neither protective nor predisposing effects. Metabolic syndrome and, increase in body weight especially, are complex side effect, and further studies is needed to increase successful exploration and identification of the genetic component and assess contribution.

Antipsychotic-induced tardive dyskinesia: The role of glutamatergic system

2016 ◽  
Vol 33 (S1) ◽  
pp. S97-S97
Author(s):  
A. Boiko ◽  
S. Ivanova ◽  
A. Semke
Keyword(s):  
Tardive Dyskinesia ◽  
Glutamate Transporter ◽  
Antipsychotic Treatment ◽  
Nucleotide Polymorphisms ◽  
Antipsychotic Therapy ◽  
Drug Induced ◽  
Schizophrenic Patients ◽  
Competing Interest

Tardive dyskinesia (TD) occurs in 20–25% of patients with long-term antipsychotic therapy. Abnormalities in glutamatergic transmission are considered one of the key components of the pathogenesis of drug-induced side effects. Glutamate acts as excitotoxin under certain conditions and in excessive concentrations.Aim is to study the concentration of glutamate and analysis of single nucleotide polymorphisms (SNP) in genes coding the glutamate transporter and NMDA-receptors in schizophrenic patients with TD and without it.The study group included 156 patients with schizophrenia receiving long-term antipsychotic treatment. Patients were divided into two groups: 63 patients with TD and 93 patients without it. Glutamate was determined in serum by spectrophotometric method. Determination of allelic variants of gene SLC1A2 (rs4354668) and GRIN2A (rs2650427, rs1969060) was performed by polymerase chain reaction in real-time.We found a significant (P < 0.05) increase of the concentration of glutamate in patients with TD. Significant (P < 0.05) reduction in frequency of genotype GG of GRIN2A (rs1969060) and TT of SLC1A2 (rs4354668) were found in patients with TD in comparison to group without TD. In the study of glutamate concentration depending on the genotype GRIN2A (rs1969060) and genotype SLC1A2 (rs4354668) we observed a statistically significant change: elevated levels of glutamic acid identified with the heterozygous genotype in patients.It is possible to suggest that reduction in frequency of these genotypes increases the risk of movement disorders due to the protective effect of these genotypes.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Morphophenotypic predictor of the development of visceral obesity in patients with schizophrenia receiving antipsychotic therapy

2018 ◽  
Vol 17 (4) ◽  
pp. 54-64 ◽  
Author(s):  
E. G. Kornetova ◽  
V. V. Dubrovskaya ◽  
A. N. Kornetov ◽  
O. A. Lobacheva ◽  
S. A. Ivanova ◽  
...  
Keyword(s):  
Visceral Fat ◽  
Visceral Obesity ◽  
Statistical Processing ◽  
Antipsychotic Therapy ◽  
Russian Version ◽  
Icd 10 ◽  
Schizophrenic Patients ◽  
Student’S T ◽  
Definition Of

Objective:revealing the role of morphophenotypic indices in the development of visceral obesity in patients with schizophrenia receiving quetiapine and risperidone therapy.Materials and methods.56 indoor patients with schizophrenia who received quetiapine (n= 23) or risperidone (n= 33) at medium doses were examined. Included persons were from 18 to 65 years old with at least a 1 year history of disease, the condition of which met the criteria of schizophrenia according to ICD-10. The Basis map of sociodemographic and clinical-dynamic signs for patients with schizophrenia was filled in, PANSS in the adapted Russian version – SCI-PANSS, noninvasive bioimpedancemetry, measurement of growth, transversethoracic, biacromial and bicrystal diameter, with calculation of body mass indexes, Tanner and Rees – Eysenk and definition of integral morphophenotypic indicators were carried out. Statistical processing was performed using Student’s t-test with a preliminary estimate of Pearson’s χ2 normal distribution, the Mann – Whitney U test to compare independent samples, the Spearman correlation analysis, the two-sided Fisher test.Results.There were no significant differences in both subgroups in terms of bioimpedancemetry. The correlation between the level of visceral fat and the Rees – Eysenk index in patients receiving risperidone was a moderate inverse: the greater the value of the Rees – Eysenk index, the lower the level of visceral fat (r= –0.73381,t= –4.70833,p= 0.00015). The correlation between the Tanner index and the level of visceral fat in the quetiapine subgroup was strong: the larger the Tanner index, the higher the visceral fat level (r= 0.7763,t= 4.08481,p= 0.00181); in the risperidone subgroup, there was an average direct correlation (r= 0.48133,t= 2.39356,p= 0.02716).Conclusion.The magnitude of the Rees – Eysenk index of schizophrenic patients can be considered among other factors in the management of risperidone in individuals with asthenic physique. The determination of the Tanner index at the beginning of treatment can play the role of a prognostic factor in the development of visceral obesity in patients with schizophrenia in the planned use as a basic therapy for quetiapine.

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