The Plasma Levels of hsa-miR-19b-3p, hsa-miR-125b-5p, and hsamiR- 320c in Patients with Asthma, COPD and Asthma-COPD Overlap Syndrome (ACOS).

BACKGROUND: Bronchial Asthma (BA) and Chronic Obstructive Pulmonary Disease (COPD) are chronic airway inflammation diseases. In recent years, patients with signs of both BA and COPD have been assigned to a separate group as Asthma-COPD Overlap Syndrome (ACOS). Free-circulating plasma microRNAs are considered as potential biomarkers of pulmonology diseases, including BA, COPD, and ACOS. OBJECTIVE: This study aimed to investigate the expression level of free-circulating plasma microRNAs, hsa-miR-19b-3p, hsa-miR-125b-5p, and hsa-miR-320c in patients with BA, COPD and ACOS for the detection and validation of new microRNAs as biomarkers for chronic lung diseases. METHODS: The relative expression levels of 720 microRNAs were evaluated by Real Time-Polymerase Chain Reaction (RT-PCR) in patients with COPD and BA. Three upregulated microRNAs (hsa-miR-19b-3p, hsa-miR-125b-5p and hsa-miR-320c) were selected for further study. The obtained data were analyzed using the microRNA PCR Array Data Analysis tool. The sensitivity and specificity were estimated using the area under the Receiver Operating Characteristics curve (ROC). RESULTS: The expression level of free-circulating hsa-miR-19b-3p was decreased in the blood plasma of patients with BA and ACOS, and increased in patients with COPD. hsa-miR-125b-5p was downregulated in the blood plasma of patients with COPD and upregulated in patients with BA and ACOS. hsa-miR-320c was downregulated in the blood plasma of patients with BA, and upregulated in patients with COPD and ACOS. The ROC curves of patients with BA for hsa-miR-19b-3p, patients with ACOS for hsa-miR-125b-5p, and patients with COPD for hsa-miR-320c revealed the probability of them as valuable biomarkers with AUCs of 0.824, 0.825, and 0.855, respectively. CONCLUSION: Our study revealed three promising biomarkers for the diagnosis of COPD, BA and ACOS.

The Relationship between Cytokine Profile and Hypertension among the Mercury-Exposed Residents of Temirtau Region in Central Kazakhstan.

BACKGROUND: Mercury is a common environmental contaminant and it is also harmful to human health. Among reported toxicities, its harmful effect on hypertension is poorly documented. In Kazakhstan, Temirtau city has been reported to have a high level of mercury contamination from an acetaldehyde production factory. Therefore, we aimed to investigate the association between serum profile of cytokines and the development of hypertension among the exposed citizens. METHODS: We selected 81 individuals for study, out of them, 41 exposed ones suffered hypertension and 40 - unexposed healthy controls in villages Chkalovo, Samarkand, Gagarinskoye, Tegiszhol, Rostovka in 2016. Mercury content in urine was studied by inversion voltammetry. Cytokine levels of IL-2, IL-6, IL-10 and TNF-α were determined by ELISA. RESULTS: Mercury-exposed citizens, especially those with hypertension, had significantly higher concentrations of inflammatory cytokines TNF-α, IL-2, IL-6 and anti-inflammatory cytokine IL-10 as compared to the unexposed population. The dependence of the mercury level in urine on IL-2 content was also detected. Therefore, chronic low doses of exposure to mercury were associated with an increase in serum levels of immune markers and with the increased risk of hypertension. CONCLUSION: The presence of mercury in the body probably affected the expression of interleukin-2, one of the main cytokines that coordinate immune response.

An investigation of the association between ADRB2 gene polymorphisms and asthma in Kazakh population.

INTRODUCTION: Beta-2-adrenergic receptor (ADRB2) is present in the cells of the respiratory tract, including bronchial smooth muscle cells and bronchial epithelium, and is a target for endogenous catecholamines and drugs used to treat the obstructive lung diseases. OBJECTIVES: This study aimed to investigate the possible association of the Arg16Gly and Gln27Glu polymorphisms of the ADRB2 gene with asthma and its endophenotypes in the Kazakh population. METHODS: A total of 70 asthmatic patients and 80 healthy controls were genotyped for Arg16Gly and Gln27Glu polymorphisms of the ADRB2 gene by using quantitative real-time polymerase chain reaction. Statistical analysis was performed with the Graph Pad InStat 7 Software. RESULTS: No associations between the asthma patients and healthy individuals were found when the allele and genotype distribution of Arg16Gly and Gln27Glu single nucleotide polymorphisms were compared. Analysis of the haplotype frequencies showed statistically significant differences between patients with asthma and controls for Arg16Gly/Gln27Gln and Arg16Gly/Gln27Glu haplotypes (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 0.87-5.16 and OR = 2.25, 95% CI = 0.89-5.67 respectively). The Arg16 allele and Arg16Arg genotype frequencies were higher in patients with uncontrolled asthma than in controls (χ2 = 5.17, df = 1, P = 0.02 and χ2 = 5.36, df = 1, P = 0.02 respectively). CONCLUSION: The results of this study support the possible involvement of Arg16Gly polymorphism in the development of uncontrolled asthma, and indicate that Arg16Gly/Gln27Gln and Arg16Gly/Gln27Glu haplotypes are more common in asthma patients in the Kazakh population.

The Potential Role of miRNA-19b-3p and miRNA-320c in Patients with Moderate Bronchial Asthma.

BACKGROUND: Bronchial Asthma (BA) is a complex heterogeneous disease with a number of molecular immunopathological mechanisms underlying airway inflammation, hyperreactivity, and bronchial remodeling. MicroRNAs are important regulators in the pathogenesis and progression of chronic respiratory diseases, including BA. OBJECTIVE: The aim of the study is to investigate the level of expression of cell-free circulating miR-19b-3p and miR-320c in the blood plasma by comparing their plasma levels with IL-4 in the moderate BA patients and control group. METHODS: The level of expression miR-19b-3p and miR-320c were evaluated by qRT-PCR using the comparative threshold cycle (Ct) method. U6 small nuclear RNA was taken as an endogenous control. The content of IL - 4 in blood plasma was determined by using ELISA. RESULTS: miR-19b-3p and miR-320c were significantly dysregulated in moderate asthmatic patients in comparison with control group. The area under the ROC curve of miR-19b-3p and miR-320c showed 0.8088 (95% CI 0.6925 to 0.9251, P value =0.0001) and 0,9048 (95% CI 0,7792 to 1,000, P value <0,0001), respectively. BA patients showed a considerably positive correlation between the expression level of microRNA-320c and IL-4 levels. CONCLUSION: These cell-free circulating microRNAs are probably deregulated in other inflammatory/ pathological diseases, so they could be useful to understand the molecular pathogenesis of BA or to investigate the "inflammatory reaction" in this disease.

EPHX1 Y113H polymorphism is associated with increased risk of chronic obstructive pulmonary disease in Kazakhstan population.

Chronic obstructive pulmonary disease (COPD) is a type of obstructive lung disease characterized by long term poor airflow which worsens over time. It is considered to be one of the top five chronic diseases of the world in terms of morbidity and mortality. Genetic variability has been found to contribute to the development of COPD. Although association between gene polymorphisms in EPHX1 and TNF-a genes and chronic obstructive pulmonary disease (COPD) have been found but till date no genetic association studies have been done in the COPD affected Kazakhstan population. The aim of the present work was to investigate the association between the Y113H polymorphism (rs1051740) in EPHX1 gene and -308G/A polymorphism (rs1800629) in TNF-a gene and COPD in Kazakhstan population. A case-control study was conducted in Astana and Akmola regions of Kazakhstan, involving 55 cases with COPD and 52 healthy individuals who served as the controls. The polymorphisms were determined using conventional PCR and Sanger sequencing method. Results show that for the EPHX1 gene Y113H polymorphism, the presence of an "C" allele (TC/CC genotype) was significantly overrepresented in the COPD patients compared to the controls. For the TNF-a gene -308G/A polymorphism, no significant difference was found between the two groups. Thus we found that, Y113H polymorphism in EPHX1 gene contributed to increased susceptibility to COPD in the Kazakhstan population.