EVALUATION OF THE PLASMA MICRO RNA EXPRESSION LEVELS IN SECONDARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life threatening hyper inflammatory disease. Micro RNAs (miRNA) are about 22 nucleotide-long, small RNAs encoded with genes, and they have regulatory functions in immune response. Objective: To determine the miRNA expression levels of 11 secondary HLH patients, we evaluated the associations of miRNA levels with pathogenesis, clinical presentation, and prognosis of the disease. Patients and Methods: Patients who were diagnosed with secondary HLH from January 2011 to December 2012 were included in this study. We profiled the expressions of 379 miRNAs in plasma of both HLH patients and healthy controls. Patients were evaluated regarding with age, clinical findings, miRNA expresions, laboratory data, treatment, and prognosis, by using descriptive statistics. Results: A total of 11 secondary HLH patients and 11 healthy children were included in this study. miR-205-5p was expressed in all case and controls and expression level of miR-205-5p was found 6.21 fold higher than control group (p=0.01). We detected the second highest expression percent in miR-194-5p with 81% of cases and controls. Expression level of miR-194-5p was found to have 163 fold higher than controls (p= 0.009). miR-30c-5p showed 77% expression percent in cases and controls together. The expression level of this miRNA was detected 9 fold decreased in HLH patients compared to healthy children (p= 0.031). Conclusion: We showed that miR-205-5p, miR-194-5p and miR-30c-5p could be useful plasma biomarkers for HLH. Further research is needed in larger and homogenous study groups, especially for these miRNAs as biomarkers for HLH.

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The Effect of Micro RNA-34a and carboplatin combination on the inducing apoptosis of Breast Cancer Cell line

10.21203/rs.3.rs-289066/v1 ◽

2021 ◽

Author(s):

Sajjad Eslamkhah ◽

Nazila Alizadeh ◽

Sahar Safaei ◽

Mohammad Amini ◽

ahad Mokhtarzadeh ◽

...

Keyword(s):

Breast Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Cell Line ◽

Caspase 3 ◽

Cancer Cell Line ◽

Micro Rna ◽

Control Group ◽

Expression Levels ◽

Micro Rnas

Abstract Aim: Breast cancer (BC) has been classified among the main causes of death owing to females' cancer. Carboplatin is a platinum-based chemotherapeutic drug that is an important treatment option for BC. But high and frequent doses of carboplatin usually reducing the reaction of cancer cells to medication. There is an immediate need to establish methods for increasing the carboplatin susceptibility to BC cells. For instance, micro RNAs (miRNAs) such as MiR34a demonstrate significant potential. Considering that, this research was planned to explore the better clinical effect and underlying mechanism of miR-34a as a possible tumor inhibitor and drug resistance regulator in compound with carboplatin chemotherapy drug in the cell lines of BC in humans. Methods: MCF-7 cell line was transfected with miR-34a to perform functional analyses. Subsequently, the MTT assay was applied to assess cell viability. Cell viability and cell death associated gene expression amounts including Bax, Bcl-2, caspase-3, MDR1, P53, and mir34-a, were examined through real-time quantitative PCR. Results: Findings showed that miR-34a upregulation significantly decreased MCF7 cell viability in comparison with control group. Furthermore, separate treatment of cells with miR-34a mimics and carboplatin could significantly increase Bax, Caspase-3, P53, and decrease in Bcl-2 mRNA expression levels evaluated to the non-treated group. Moreover, by reduction in expression levels of the MDR1 gene, BC cells' reaction to carboplatin has increased via miR-34a. Conclusion: In line with the findings, it could be inferred that miR-34a may improve the responsiveness of breast cancer cells to carboplatin chemotherapy with downregulation of MDR1.

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The Clinical Significance of Changes in the Expression Levels of MicroRNA-1 and Inflammatory Factors in the Peripheral Blood of Children with Acute-Stage Asthma

BioMed Research International ◽

10.1155/2018/7632487 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Man Tian ◽

Ying Zhou ◽

Haoyuan Jia ◽

Xuming Zhu ◽

Yubao Cui

Keyword(s):

Disease Severity ◽

Clinical Significance ◽

Peripheral Blood ◽

Acute Stage ◽

Expression Level ◽

Inflammatory Factors ◽

Control Group ◽

Study Group ◽

Healthy Children ◽

Expression Levels

This study assessed the changes and clinical significance of microRNA-1 (miR-1) and inflammatory factors in the peripheral blood of children with acute-stage asthma. 100 children with acute-stage asthma (study group) and 100 healthy children (control group) were enrolled. For all enrolled children, the peripheral blood levels of miR-1, interleukin-4 (IL-4), IL-5, IL-8, tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ) were measured. The relative expression levels of miR-1 and IFN-γ in the peripheral blood of children in the study group were significantly lower than those in the control group, whereas expression levels of IL-4, IL-5, IL-8, and TNF-α were significantly higher. Moreover, these levels changed to a greater extent in patients with severe disease (P < 0.05). Further analyses showed that the miR-1 expression level positively correlated with IFN-γ and negatively correlated with IL-4, IL-5, IL-8, and TNF-α expression levels (P < 0.05). ROC curve analysis to identify diagnostic specificity and sensitivity showed that, for diagnosing exacerbation in asthma, the area under the curve (AUC) for miR-1 was the highest (AUC = 0.900, P < 0.05) of all tested markers; this held true for diagnosing severe asthma as well (AUC = 0.977, P < 0.05). Compared to healthy children, children with acute-stage asthma had a low miR-1 expression level and a Th1/Th2 imbalance in their peripheral blood. The changes were closely related, became more exaggerated with an increase in disease severity, and could be used as auxiliary variables for diagnosing asthma exacerbation and evaluating disease severity.

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Prostate-Specific antigen value and micro RNAs as potential diagnostic biomarkers for prostate cancer

Medical Science and Discovery ◽

10.36472/msd.v8i2.479 ◽

2021 ◽

Vol 8 (2) ◽

pp. 107-113

Author(s):

Aydemir Asdemir ◽

Sevgi Durna Dastan ◽

Esat Korgali ◽

Tugba Yildiz Asdemir ◽

Huseyin Saygin ◽

...

Keyword(s):

Prostate Cancer ◽

Specific Antigen ◽

Diagnostic Value ◽

Micro Rna ◽

Control Group ◽

Diagnostic Biomarkers ◽

Expression Levels ◽

Non Invasive ◽

Cancer Group ◽

Micro Rnas

Objective: It is necessary to provide PSA alternatives or methods that can be used in conjunction with PSA to regress complications rising from negative biopsies and to increase diagnostic value. Patients and Methods: The study is consisting of 59 men as the sample group. Blood samples from the individuals are grouped as prostate cancer and BPH (benign prostatic hyperplasia) groups. 27 prostate cancer patients whom some of them also operated are assembled in the patients group and the other 32 individuals are grouped as BPH group. Micro RNA expression levels evaluated by RT-PCR. Results: Prostate cancer group when compared with the control group, it is observed that expression levels of miRNA-221 and miRNA-432 increased while expression levels of miRNA-17-5p, miRNA-30c, miRNA-107, miRNA-141, miRNA-145, miRNA-181a-2, miRNA-331-3p, miRNA-574-3p decreased and expression levels of miRNA-21 and miRNA-375 are quite similar between the groups. Conclusion: The prospect of strong and sensitive serum miRNA expression levels in prostate cancer cases which are easily detectable by non-invasive methods as biomarkers is a promising field of study. Nevertheless, it is currently necessary to work in conjunction with both tissue and serum to enhance both sensitivity and specificity of miRNAs as biomarkers. As such, expression levels of the same miRNAs in tissue and serum provide different expression values which in turn make it difficult to indicate a common biomarker.

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POS0191 THE VALUE OF MIR-20B, MIR-22, MIR-26A, MIR-125B AND MIR-221 IN RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.443 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 309.1-310

Author(s):

M. Ciesla ◽

B. Kolarz ◽

M. Majdan ◽

M. Dryglewska

Keyword(s):

Rheumatoid Arthritis ◽

Rheumatoid Factor ◽

Micro Rna ◽

Clinical Variable ◽

Tender Joint Count ◽

Control Group ◽

Altered Expression ◽

Expression Levels ◽

Das 28 ◽

Micro Rnas

Background:Micro-RNAs (miRNAs) are an endogenous small, single-stranded, non-coding RNAs with a 18-25 nucleotide long and have been reported as a potential extracellular biomarkers of various diseases. They mainly decrease the gene expression by inhibiting the translation or cause mRNA destabilization.Objectives:The aim of the study was to identify miRNAs whose plasma expression level is associated with RA prevalence and/or activity.Methods:A total of 74 unrelated individuals, 50 with RA and 24 in a control group were enrolled to the study. Real-time PCR was used to evaluate the plasma expression levels of 5 miRNAs: miR-20b, miR-22 miR-26a, miR-125b, miR-221.Results:We found the differences in four out of five evaluated miRs between RA and HC group – miR-26a, p<0.0001; miR-125b, p <0.0001; miR-20b p<0.0001; miR-22, p=0.005. Graphical presentation of the results is shown in Figure 1. The logistic regression results showed that miR-22 (p=0.0003) and miR-26a (p=0.049) are the most important molecules distinguishing RA patients and healthy controls in the study. MiR-22 was positively correlated with ESR (rs=0.41), CRP (rs=0.49) and DAS28 (rs=0.33) and miR-26a was positively correlated with ESR (rs=0.49), CRP (rs=0.41), number of swelling joints (rs=0.43), number of painful joints (rs=0.74) and DAS28 (rs=0.63). Moreover, miR-22 expression was different between rheumatoid factor (RF) positive and RF negative patients (p=0.04).Conclusion:The results showed that miR-22 (p=0.0003) and miR-26a (p=0.049) may be the most useful in evaluated panel of miRs distinguishing RA patients and HCs. In this study we demonstrated for the first time that plasma concentration of miR-22 may be considered as a potential molecular marker of RA exacerbation.References:[1]Ouboussad, L., Hunt, L., Hensor, E.M.A. et al. Profiling microRNAs in individuals at risk of progression to rheumatoid arthritis. Arthritis Res Ther 2017 19, 288.[2]Churov AV, Oleinik EK, Knip M. MicroRNAs in rheumatoid arthritis: altered expression and diagnostic potential. Autoimmun Rev. 2015 14(11):1029-37.Figure 1.Diagrams from A to D show the expression levels of miR-22, miR-26a, miR-125b and miR-20b, respectively. The median values of expression have been connected by a line.Table 1.Spearman’s rank correlation between micro-RNA-22 and micro-RNA-26 and the clinical variables.miRs \ clinical variableAgeDisease durationESRCRPSJCTJCDAS-28ACPARFmiR-220.09-0.270.410.490.260.210.330.240.16miR-26a0.20.140.490.410.430.740.630.260.16The significant correlations were bolded and indicated by red. Abbreviations: ACPA, anti-citrullinated protein antibodies; CRP, C-reactive protein; SJC, swollen joint count; TJC, tender joint count; DAS-28, disease activity score 28; ESR, erythrocyte sedimentation rate; RF, rheumatoid factor.Disclosure of Interests:None declared

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Analysis of Let-7a and Mir-17-5p Micro-RNAs Expression In Patients with Adult De Novo Myelodysplastic Syndromes

Blood ◽

10.1182/blood.v116.21.4965.4965 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4965-4965

Author(s):

D. Vassilatou ◽

Vassiliki Pappa ◽

F. Kontsioti ◽

S. Papageorgiou ◽

C. Kontos ◽

...

Keyword(s):

Bone Marrow ◽

Myelodysplastic Syndromes ◽

Small Sample ◽

Micro Rna ◽

Clinicopathological Parameters ◽

Control Group ◽

Ras Proteins ◽

Expression Levels ◽

Micro Rnas ◽

Cd34 Cells

Abstract Abstract 4965 Introduction. MicroRNAs are small non-coding RNAs that act at the post-transcriptional level, regulating protein expression by repressing translation or destabilizing mRNA target. Since their discovery, microRNAs have been associated with almost every normal cell function, including proliferation, differentiation and apoptosis. Several studies suggest that they have an important role in normal hematopoiesis and hematological malignancies. Let-7a negatively regulates the expression of Ras proteins, which are overexpressed in patients with Myelodysplastic syndromes (MDS). In addition mir-17-5p contributes to the down-regulation of E2F1, which is overexpressed in MDS. Purpose. The purpose of the current study was to evaluate the expression of let-7a and mir-17-5p in CD34 cells from the bone marrow of patients with MDS. Material and methods. We evaluated 29 patients with MDS (25 men, 4 women) with median age 73 years. FAB classification was as follows: 9 RA, 15 RAEB, 2 RAEB-t and 3 AML. According to IPSS our study included 9 patients with low, 8 with Int-1, 7 with Int-2 and 5 with high risk disease. We isolated CD34+ cells from bone marrow of patients using magnetic beads. Extraction of microRNA and total RNA was performed and cDNA of let-7a and mir-17-5p was amplified using real time PCR, to study the relative expression of these microRNAS according to the expression of RNU48 (a snoRNA used as control). The control group included donors of CD34+ cells for stem cell transplantation. Results. The median miR17-5p expression level in patients was lower compared to controls [23vs 47.4]. The median let-7a expression levels were higher in MDS patients than in healthy donors [32.85 vs 8]. However these differences were not significant as shown by the Mann-Whitney U test. Moreover, ROC analysis demonstrated that neither miR17-5p nor let-7a expression had significant discriminatory value to efficiently distinguish MDS patients from non-MDS. In addition Spearman analysis did not reveal any correlations between these two microRNA expression levels and other continuous variables examined in the current study (age, hemoglobin concentration, numbers of neutrophils, platelets, and BM blasts). Finally, we found no associations between either miR17-5p or let-7a expression and clinicopathological parameters of MDS patients using chi-square (χ2) or Fisher's exact test where appropriate. Conclusion. The micro RNA let-7 was overexressed although not significantly in CD34 cells from MDS patients demonstrating that this is not a mechanism contributing to the increased expression RAS proteins in MDS. The micro RNA-mir17-5 is underexpressed in CD34 cells and needs further investigation for the establishment of a role in the overepxression of E2F in MDS. The lack of significant differences in the expression levels of both micro RNAs could be related to the admixture of normal and dysplastic CD34 cells in the bone marrow of MDS or to the small sample size. Disclosures: No relevant conflicts of interest to declare.

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Identification and Validation of Serum Autoantibodies in Children with B-cell Acute Lymphoblastic Leukemia by Serological Proteome Analysis

10.21203/rs.3.rs-867969/v1 ◽

2021 ◽

Author(s):

Runhong Yu ◽

Shiwei Yang ◽

Yufeng Liu ◽

Zunmin Zhu

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Western Blot ◽

B Cell ◽

Lymphoblastic Leukemia ◽

Immunohistochemical Analysis ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Healthy Children ◽

Expression Levels ◽

Cell Acute Lymphoblastic Leukemia

Abstract Purpose: Study was by intention to screen serum autoantibodies that may contribute to the early detection of B-cell acute lymphoblastic leukemia (B-ALL) in children.Patients and methods: The total protein from three pooled B-ALL cell lines(NALM-6, REH and BALL-1 cells) was separated using two-dimensional gel electrophoresis(2-DE), which was followed by Western blot by mixed serum from B-ALL patients (n=20) or healthy children(n=20). We obtained and analyzed the images of 2-D gel and Western blot by PDQuest software,and then identify the spots of immune responses in B-ALL samples compared with those in control samples.The proteins from spots were identified using mass spectrometry (MS). The autoantibodies against α-enolase and voltage-dependent anion-selective channel protein 1(VDAC1) were further validated on the use of enzyme-linked immunosorbent assay(ELISA). The protein expression levels of the candidate antigens α-enolase and VDAC1 in B-ALL were thoroughly studied by immunohistochemical analysis.Results: Six protein dots were identified with MS as Aconitase,apoptosis-inducing factor(AIF),dihydrolipoamide dehydrogenase(DLD), α-enolase,medium-chain acyl-CoA dehydrogenase(MCAD) and VDAC 1.The frequencies of autoantibodies against α-enolase and VDAC1 in children with B-ALL were 27% and 23%, respectively, which were significantly higher than those in normal controls(4% and 0). Immunohistochemical analysis showed the expression of α-enolase and VDAC1 was positive in 95% and 85% of B-ALL patients, respectively, but negative expression levels were showed in the control group. Conclusion: This study incidates that α-enolase and VDAC1 may be the antigen associated with B-ALL .α-enolase and VDAC1 autoantibodies may develop into potential serological markers of B-ALL in children.Other proteins also need to be confirmed in a large number of serum samples.

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ATF3 and EGR2 gene expression levels in sdLDL-treated macrophages of patients with coronary artery stenosis

LaboratoriumsMedizin ◽

10.1515/labmed-2017-0138 ◽

2018 ◽

Vol 42 (1-2) ◽

pp. 23-29

Author(s):

Sayed R. Hosseini-Fard ◽

Mohsen Khosravi ◽

Amaneh Yarnazari ◽

Parisa Hassanpour ◽

Abdollah Amirfarhangi ◽

...

Keyword(s):

Gene Expression ◽

Coronary Artery ◽

Cholesterol Metabolism ◽

Quantitative Polymerase Chain Reaction ◽

Fold Change ◽

Expression Level ◽

Control Group ◽

Expression Levels ◽

Vessel Disease ◽

Gene Expression Levels

AbstractBackground:The metabolism of cholesteryl esters (CEs) is under the control of a gene network in macrophages. Several genes such asATF3andEGR2are related to cholesterol metabolism.Methods:In this study, theATF3andEGR2gene expression levels were evaluated in differentiated macrophages of subjects undergoing coronary artery angiography [controls (<5% stenosis), patients (>70% stenosis)] after treatment with small dense low density lipoprotein (sdLDL) particles. Monocytes were isolated using a RosetteSep Kit and were differentiated into macrophages using the M-CSF factor. A modified heparin-MgSO4-PEG method was used for the sdLDL preparation. TheATF3andEGR2gene expression levels were measured by the real-time quantitative polymerase chain reaction (RT-qPCR) technique.Results:In contrast with the control group (p=0.4), theATF3expression level reduced significantly in the differentiated macrophages from all patients [single vessel disease (SVD), fold change 17 times, p=0.02; two vessel disease (2VD), fold change 1.5 times, p=0.05; three vessel disease (3VD), fold change 3.5 times, p=0.04]. Also, theEGR2expression level reduced significantly in all groups (p<0.02). The gene fold changes had no significant differences between the patients (p>0.8).Conclusions:We propose that the failure ofATF3gene expression improves the CE synthesis after sdLDL influx. Furthermore, the reducedEGR2gene expression level in the sdLDL-treated groups may be a negative factor in cholesterol homeostasis.

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Hsa-miR-27a-3p overexpression in men with nonobstructive azoospermia: A case-control study

International Journal of Reproductive BioMedicine ◽

10.18502/ijrm.v13i11.7963 ◽

2020 ◽

Author(s):

Hamid Norioun ◽

Majid Motovali-bashi ◽

Seyed Morteza Javadirad

Keyword(s):

Male Infertility ◽

Case Control Study ◽

Quantitative Polymerase Chain Reaction ◽

Case Control ◽

Micro Rna ◽

Expression Level ◽

Obstructive Azoospermia ◽

Aberrant Expression ◽

Micro Rnas ◽

Control Study

Background: The role of KDM3A and its downstream genes in male fertility has been approved in animal models. Additionally, the expression shrinkage of KDM3A is significantly correlated with human azoospermia phenotype. Aberrant expression of micro-RNAs could mislead spermatogenesis and mostly lead to diverse phenotypes of male infertility. Objective: The aim of this study was to evaluate the expression level of hsa-miR-27a- 3p in azoospermic men to reveal its possible association with infertility. Materials and Methods: This case-control study was conducted on 30 azoospermic men, of whom, 19 had non obstructive azoospermia (NOA) and 11 obstructive azoospermia (OA) according to the pathological examinations. Comprehensive bioinformatics investigations were performed securely and hsa-miR-27a-3p was selected afterward. Reverse Transcriptase-quantitative polymerase chain reaction (RTqPCR) method was used and statistical analysis was performed to compare the expression level of hsa-miR-27a-3p in both OA and NOA individuals. Results: In silico analysis suggested hsa-miR-27a-3p, with its potential binding ability to target KDM3A transcripts. The expression analysis of candidate hsa-miR-27a-3p indicated its significant overexpression in NOA men. Conclusion: The hsa-miR-27a-3p was overexpressed in NOA men compared to OA-control individuals. As a consequence, the overexpressed micro-RNA could downregulate directly KDM3A and indirectly TNP1 and PRM1. Therefore, spermatogenesis could be misled and male infertility could be developed. Key words: hsa-miR-27a-3p, Male infertility, KDM3A.

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Correlation of Vitamin D3 with the Expression of RORγt and Foxp3 mRNAs in the Peripheral Blood of Myasthenia Gravis Patients

NeuroImmunoModulation ◽

10.1159/000510861 ◽

2020 ◽

pp. 1-7

Author(s):

Pan Huang ◽

Xiao-ying He ◽

Min Xu

Keyword(s):

Myasthenia Gravis ◽

Peripheral Blood ◽

Normal Subjects ◽

Orphan Receptor ◽

Expression Level ◽

Control Group ◽

Foxp3 Mrna ◽

Expression Levels ◽

Relative Expression ◽

The Relationship

Objectives: to investigate the expression levels of 1,25(OH)2D3 in the peripheral blood from patients with myasthenia gravis (MG) and to correlate levels with retinoid-related orphan receptor γt (RORγt) and forkhead or winged-helix transcription factor 3 (Foxp3) mRNA expression. Methods: Sixty-seven patients with MG were enrolled in the experimental group, and 50 normal subjects were selected as the control group. The expression levels of 1,25(OH)2D3 and RORγt and Foxp3 mRNAs were measured in the serum of the 2 patient groups and the relationship between factors were correlated with the severity score of MG. The relationship between the levels of 1,25(OH)2D3 and the relative expressions of RORγt and Foxp3 mRNAs was determined. Results: There were no differences between groups regarding patient’s baseline data. 1,25(OH)2D3 and RORγt and Foxp3 mRNAs are differentially expressed in the MG group and the control group (p < 0.05). QMG score is negatively correlated with the expression level of peripheral blood 1,25(OH)2D3 and Foxp3 mRNA (r = −0.797, −0.543; p < 0.01) and positively correlated with the relative expression level of RORγt mRNA (r = 0.539; p < 0.01). 1,25(OH)2D3 expression level was negatively correlated with the relative expression of RORγt mRNA (r = −0.559; p < 0.01) and positively correlated with the relative expression of Foxp3 mRNA (r = 0.390; p < 0.01). Conclusions: The levels of 1,25(OH)2D3 were shown to be lower in patients with MG compared to normal controls. The observed low levels of 1,25(OH)2D3 may lead to changes in the expression of RORγt and Foxp3 mRNAs involved in MG.

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P1811GENETIC POLYMORPHISMS IN STAT4, VEGF2578 AND PTPN22 GENES IN CHILDREN WITH GLOMERULOPATHIES

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1811 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Ina Kazyra ◽

Alexandr Sukala ◽

Hanna Bialkevich ◽

Anna Krylova-Alefirenko ◽

Natalia Tur ◽

...

Keyword(s):

Lupus Erythematosus ◽

Polymorphic Locus ◽

Pediatric Nephrology ◽

Study Groups ◽

Minor Allele ◽

Statistical Testing ◽

Control Group ◽

Healthy Children ◽

Glomerular Diseases ◽

Significant Difference

Abstract Background and Aims Glomerular diseases (GD) often have genetic predisposition, especially those autoimmune or immune complex-mediated. Our aim was to assess an impact of genetic polymorphism in STAT4 rs7574865 and rs3821236, VEGF rs699947 and PTPN22 rs2476601 on the risk of development of primary (PG) and secondary (SG) glomerulopathies in children. Method We enrolled 81 child with GD (m:f 33/48) and 335 healthy controls (m:f 184/151). Patients of the study group were arranged into two groups: 1st - with PG (38 children aged 3-17 yrs, 13±3,45, m:f 22/16) and 2nd - with SG (43 children aged 7-17 yrs, 13±3,59, m:f 11/32). 1st group included 35 patients with hereditary nephritis, 2 with IgA nephropathy, 1 – FSGS. 2nd group included 10 patients with ANCA associated vasculitis, 11 with IgA vasculitis, 22 with systemic lupus erythematosus (SLE). These patients were identified and monitored at the National Center for Pediatric Nephrology. Control group (CG) was matched with the study groups for age and sex and included 335 healthy children (m:f 184/151, age 2-17 yrs, 14,28±2,56). We analyzed DNA by polymerase chain reaction for identification of genotypes. Results The frequency of genotypes and allels for STAT4 rs 7574865 was found to be GG 55,26% in 1st, 46,51% in 2nd versus (vs) 62,09% in CG; GT 39,47%, 41,86% vs 32,24%; TT 5,26%, 11,63% vs 5,67%; for minor allele T 25,00%, 32,60% vs 21,79%, respectively. For STAT4 rs3821236: GG found in 65,79% in 1st, 55,81% in 2nd vs 65,07% in CG; GA genotype in 26,32%, 41,86% and 30,15%; AA genotype in 7,89%, 2,33% and 4,78%; minor allele A in 21,05%, 23,26% and 19,85%, respectively. For VEGF2578 rs 699947: AA 28,95% in 1st, 30,23% in 2nd vs 20,30% in CG; AC 44,74% and 51,16% vs 57,31%; CC 26,32% and 18,60% vs 22,39%; minor allele C 48,68%, 44,19% vs 51,04% in 1st and 2nd vs CG, respectively. For PTPN22: CC 68,42% in 1st, 59,46% in 2nd vs 72,95% in CG; CT 28,95%, 35,14%, 24,59%; TT 2,63%, 5,41% and 2,46%; minor allele T in 17,11%, 22,97% vs 14,75% in 1st,2nd and CG, respectively. The distribution of genotypes observed was tested with the Hardy-Weinberg Equilibrium. There were no differences found in rates of polymorphic genotypes in CG and patients with GD. For PTPN22 rs 2476601 and VEGF2578 rs6999467 no statistically significant difference between children of 1st, 2nd and CG was observed. We found the difference between patients with GD and healthy children (HC) for minor allele T of STAT4 rs7574865 (OR [95%CI]=1,73 [1,06-2,82], p=0,03), which was most prominent for female patients with SG (OR [95%CI]=2,31 [1,3-4,12], p=0,005). The development of SG was associated with the presence of GT+TT genotype (vs GG genotype) of STAT4 rs7574865 (OR=4,92; 95% CI [2,62-9,23]; p<0,001). Statistical testing showed significant differences between healthy female controls and SLE females for minor allele T of STAT4 rs7574865 (OR [95%CI]=2,14 [1,07-4,27], p=0,04) and GT+TT genotypes vs GG genotype of STAT4 rs7574865 (OR=2,54; 95%CI[1,00-6,42]; p<0,05). The analysis of genotypes/alleles for polymorphic locus rs3821236 of STAT4 revealed significant association of GA genotype (OR[95%CI]=2,55 [1,17-5,55], p=0,021), as well as of the sum of genotypes with at least one minor allele (GA+AA) (OR[95%CI]=3,51 [1,59-7,76], p=0,002) with the development of SG in girls. An association of the presence of the minor allele A of STAT4 rs3822136 with the likelihood of SG development in females was observed (OR[95%CI]=2,69 [1,5-4,83], p=0,001). Conclusion Minor allele T and GT+TT genotypes of STAT4 rs7574865 is associated with the risk of SG development in children and especially with the risk of SLE development in girls. Minor allele A and GA+AA genotypes of the STAT4 rs3822136 are associated with the predisposition to SG in girls. Minor allele T and GT+TT genotypes of the PTPN22 rs 2476601 are observed to be more frequent in both groups of GD and especially in girls, though failed to be statistically significant (p>0,05).

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