The effect of BclI polymorphism of NR3C1 gene on asthma phenotypes in Egyptian children

Osman, H. G.; El-kader, Karima A. Abd; Riad, Nermine Magdi; Shaaban, Hala H.; Mohamed, Noussa R.

doi:10.21608/ejpa.2020.31274.1008

Cited by 3 publications

(2 citation statements)

References 17 publications

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“…This work is licensed under the Creative Commons Attribution 4.0 International License steroids and abdominal obesity. 15,16 The presence of the minor (G) allele causes a rising sensitivity to GCs, hyperinsulinemia, increased body mass index and high distribution of abdominal fat. 17 To our knowledge, there has been no any study until now on the relationship between the BclI polymorphism of GR (NR3C1) gene and Type 2 diabetes in Iraqi society.…”

Section: Introductionmentioning

confidence: 99%

Molecular Study of Bcl1 (+647 C/G) Glucocorticoid Receptor Polymorphism of Some Iraqi Patients with Type 2 Diabetes Mellitus

2021

TJNPR

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BclI is one of the polymorphisms of glucocorticoid receptor (GR) gene that is associated with increased insulin resistance. The aim of this study was to evaluate the prevalence of Bcl1 (+647 C/G) polymorphism of the glucocorticoid receptor gene in Iraqi patients with type 2 diabetes mellitus (T2DM) and correlate it with levels of some biochemical parameters. In the study, 70 blood samples were collected from type 2 diabetic patients, and 50 blood samples from healthy individual as a control group. Biochemical parameters such as insulin, glutathione, ceruloplasmin and lipid profiles were estimated using enzymatic assays, while functional Bcl1 (+647 C/G) GR polymorphism was genotyped for both groups using a Tetra-amplification refractory mutation system polymerase chain reaction (T-ARMS PCR). The results revealed a significant increase in the levels of insulin, cholesterol and TG in the control compared with treatment groups, while there was no significant variance in the amounts of CP and HDL-C in both groups. Also, the differences in the genotype and allele frequency of Bcl1 GR polymorphism between both groups were not significant. This observation indicated a negative effect of the mutant G allele of Bcl1 GR polymorphism on T2DM patients. The finding suggests that GG genotype and allele of Bcl1 GR polymorphism may act as molecular markers of T2DM in Iraqi patients and have negative effects on insulin and other biochemical parameters.

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Section: Introductionmentioning

confidence: 99%

Molecular Study of Bcl1 (+647 C/G) Glucocorticoid Receptor Polymorphism of Some Iraqi Patients with Type 2 Diabetes Mellitus

2021

TJNPR

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“…К ведущим причинам нечувствительности относят генетические полиморфизмы гена NR3C1, которые могут приводить к экспрессии его изменению структуры доменов рецептора, его способности связываться с лигандом и молекулярными компонентами сигнальных путей[13]. Наибольшая ассоциация с тяжестью течения бронхиальной астмы и более частым возникновением устойчивости к терапии была выявлена у GG-варианта полиморфизмаBclI [18, 20,16]. Среди эффектов, вызываемых активированным глюкокортикоидным рецептором в лимфоцитах, наиболее значимым является регуляция ПКГ, что определяет важность ее изучения у пациентов с полиморфизмом, ассоциированным с резистентностью.…”

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Association of <i>NR3C1 Bcl1</i> gene polymorphism with impaired programmed cell death of lymphocytes in patients with atopic bronchial asthma

Bogomazova,

Reshetnikova,

Skibo

et al. 2023

Med. immunol.

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Atopic asthma is a chronic disease characterized by airway obstruction, bronchial hyperresponsiveness, and inflammation. Patients show increased activation of immune cells in the airways, especially T-lymphocytes, leading to chronic inflammation. The lymphocytes of asthma patients are known to have an impairment of the type 1 and 2 programmed cell death, i.e., apoptosis and autophagy, thus contributing to prolongation and intensification of inflammatory process. As compared to apoptosis, autophagy may also contribute to cell survival under stress conditions. Its disruption and hyperactivation leads to exacerbation of allergic responses. Glucocorticoids are the main drugs for the treatment of atopic bronchial asthma by activating the glucocorticoid receptor, thus triggering anti-inflammatory response and apoptosis of the cells. However, some patients exhibit resistance to therapy due to various factors, including single nucleotide polymorphisms of NR3C1 glucocorticoid receptor gene. The highest association between asthma severity and resistance to therapy was found for the GG variant of the NR3C1 Bcl1 polymorphism. Common molecular pathways for glucocorticoid receptor activation and programmed cell death and mediating molecules suggest a significant role for the polymorphic receptor variant in cell death. The aim of our study was to evaluate the effect of a single nucleotide polymorphism (G allele, i.e., Bcl1 polymorphism of NR3C1 gene) of glucocorticoid receptor on expression levels of genes that regulate apoptosis (BCL2, CASP3) and autophagy (BECN1, LC3) in lymphocytes of patients with moderate and severe atopic bronchial asthma. The study was performed with peripheral blood samples of 24 patients aged 20 to 45 years with an established diagnosis of moderate to severe atopic bronchial asthma. Using PCR technique with restriction fragment length polymorphism (RFLP) assay, the patients were distributed according to the genotypes of the BclI polymorphism of the NR3C1 gene: 12 patients with CC genotype, 8 persons with GC genotype, and 4 cases with GG genotype. The lymphocytes were isolated in Ficoll density gradient and cultivated with dexamethasone under the conditions of nutrient depletion. The level of gene expression was determined by real-time PCR. When studying associations between various genotypes of Bcl1 polymorphism and expression of cell death marker genes, the anti-apoptotic reactions were detected in lymphocytes of patients with GG polymorphism under the influence of dexamethasone thus being a potential mechanism for development of resistance to glucocorticosteroid therapy in asthma. Impaired activation of BECN1 gene expression in patients with the GG genotype may suggest deregulation of the autophagy in this group of patients, as a mode of programmed cell death. Moreover, in patients with GC genotype during long-term cultivation, exposure to dexamethasone increases the expression of the LC3 gene, indicating a more pronounced activation of autophagy. Hence, this work demonstrates differences in response of lymphocytes to synthetic glucocorticoid therapy, and probable effect of G allele (Bcl1 polymorphism) on dysregulation of programmed cell death under the influence of dexamethasone.

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Clinical And Genetic Risk Factors For Asthma Exacerbations And Mortality In Adults

Mukhtarova,

Fedorova,

Karunas

et al. 2023

Russ Open Med J

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Background — According to epidemiological studies, nearly 7 million people in Russia suffer from bronchial asthma (BA), of which 1 million have a severe form of the disease that is difficult to control. Insufficiently effective control of BA leads to a reduction in the quality of life, the development of its more severe forms, an increase in the frequency of exacerbations of the disease, and an increase in the number of disability and death cases in patients. Objective — The goal of our research was conducting a long-term cohort study of BA in adults living in the Republic of Bashkortostan and assessing the clinical and prognostic value of internal and external risk factors for exacerbation and death from BA. Methods and Results — We analyzed the medical records of 213 BA patients 18 to 67 years а age from 2012 through 2022. Genotyping of six SNPs in ADRB2 (rs1042713, rs1042714), CRHR1 (rs242939, rs1876828), NR3C1 (rs41423247), and HRH3 (rs3787429) genes was performed by real-time polymerase chain reaction. Using regression analysis, we assessed predictors of the risks of exacerbation and death in BA and built multivariate models for each outcome. Conclusion — As a result of regression analysis, significant clinical and prognostic risk factors for re-exacerbation and death from BA were identified.

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The effect of BclI polymorphism of NR3C1 gene on asthma phenotypes in Egyptian children

Cited by 3 publications

References 17 publications

Molecular Study of Bcl1 (+647 C/G) Glucocorticoid Receptor Polymorphism of Some Iraqi Patients with Type 2 Diabetes Mellitus

Molecular Study of Bcl1 (+647 C/G) Glucocorticoid Receptor Polymorphism of Some Iraqi Patients with Type 2 Diabetes Mellitus

Association of <i>NR3C1 Bcl1</i> gene polymorphism with impaired programmed cell death of lymphocytes in patients with atopic bronchial asthma

Clinical And Genetic Risk Factors For Asthma Exacerbations And Mortality In Adults

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