scholarly journals Association of eNOS (4a/4b) gene polymorphism with the development of arterial hypertension in patients with rheumatoid arthritis

2020 ◽  
Vol 4 (8) ◽  
pp. 471-474
Author(s):  
A.A. Chernova ◽  
◽  
S.Yu. Nikulina ◽  
Yu.A. Tolstokorova ◽  
◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Polymorphism ◽  
Arterial Hypertension ◽  
Molecular Genetics ◽  
Clinical Laboratory ◽  
Control Group ◽  
Enos Gene ◽  
Polymorphism Analysis ◽  
Homozygous Genotype ◽  
And Gender

Aim: to study a contribution of eNOS (4a/4b) gene polymorphism in the development of arterial hypertension (AH) in patients with rheumatoid arthritis (RA).Patients and Methods: 143 patients with RA were examined, among which a group of patients without AH (n=50) and a group of patients with RA in association with AH (n=93) were selected. Healthy volunteers (n=151) were also divided into 2 groups, comparable in age and gender to the main groups. A range of clinical, laboratory, and instrumental methods were used in this study. We also conducted molecular genetics. Blood samples were taken from all patients in the study. DNA was isolated using the phenol-chloroform DNA extraction method. Genotyping for the eNOS gene was performed by PCR-RFLP (Polymerase Chain Reaction — Restriction Fragment Length Polymorphism) analysis. PCR was performed with a set of primers to the corresponding genome regions. PCR products were analyzed by electrophoresis in a 4% polyacrylamide gel followed by staining with ethidium bromide.Results: during the molecular genetics, there was a statistically significant prevalence of 4a/4a homozygous genotype and 4a alleles of eNOS gene polymorphism in patients with RA in association with AH versus these parameters in patients with RA without AH. The estimated risk concerning odds ratio of RA occurrence in association with AH in carriers of 4a/4a genotype in the eNOS gene was 3.635 times higher versus carriers of 4a/4b and 4b/4b genotypes. 4a allele was significantly more common in the group of patients with RA in association with AH versus the control group (OR=3.458 [95% CI 1.571–4.575]; p<0.05). There were no statistically significant values in the group of patients with RA without AH versus the control group with healthy volunteers.Conclusion: 4а/4a homozygous genotype and 4a allele of the eNOS 4a/4b gene polymorphism are predictors of RA development in association with AH.KEYWORDS: rheumatoid arthritis, cardiovascular pathology, arterial hypertension, molecular genetics, single-nucleotide polymorphism, genetic association.FOR CITATION: Chernova A.A., Nikulina S.Yu., Tolstokorova Yu.A. Association of eNOS (4a/4b) gene polymorphism with the development of arterial hypertension in patients with rheumatoid arthritis. Russian Medical Inquiry. 2020;4(8):471–474. DOI: 10.32364/2587-6821-2020-4-8-471-474.

scholarly journals CYP2E1-DEPENDENT VARIATIONS IN HEPATOCYTES DAMAGE DURING TREATMENT OF TUBERCULOSIS

2019 ◽  
Vol 16 (3) ◽  
pp. 20-26
Author(s):  
L.V. Natrus ◽  
L.V. Gayova ◽  
O.O. Gorkunenko ◽  
P.A. Chernovol ◽  
M.V. Zelinska
Keyword(s):  
Gene Polymorphism ◽  
Maintenance Therapy ◽  
Genomic Dna ◽  
Clinical Laboratory ◽  
Intensive Therapy ◽  
Venous Blood ◽  
Control Group ◽  
Drug Induced ◽  
Cyp2e1 Gene ◽  
Tb Treatment

Relevance. Investigation of polymorphism in a locus of CYP2E1 as the prognostic factor of drug-induced hepatotoxicity at anti-TB therapy is significant due to the influence of CYP2E1 on drug metabolism. The objective of the investigation is to analyze the association of rs2070676 СYP2E1 gene polymorphism with drug-induced hepatotoxicity by means of the clinical-laboratory values of serum transaminases at anti-TB treatment. Materials and methods. The study involved 47 patients with drug-susceptible tuberculosis first time discovered. 58 healthy volunteers comprised a control group. Laboratory indices were determined in venous blood three times: before the treatment as baseline; in 2 months of intensive therapy (isoniazid, rifampicin, ethambutol, pyrazinamide), then in 4 months of maintenance therapy (isoniazid, rifampicin). Serum activities of enzymes ALT, AST, and GGT were measured by standard algorithm on automatic analyzer BS-300. Analysis of rs2070676 polymorphism of CYP2E1 gene was performed by polymerase chain reaction using standard PureLink® Genomic DNA Kit for Purification of Genomic DNA; Manufacturer of INVITROGEN (USA). For statistical processing, IBM SPSS Statistics 23 was applied. Results. Investigation of serum ALT and AST in patients with major genotype CYP2E1 (C/C) showed the lower baseline ALT and AST levels comparing to the control group, which might be caused by suppression of hepatocytes functions at the development of the disease. Anti-TB treatment caused an increase in ALT and AST levels comparing to the baseline in patients with major CYP2E1 (C/C) genotype. In the group with C/G polymorphism, the baseline ALT level didn’t differ much from the baseline of the control group; it showed a decrease after intensive therapy and returned back to the initial level at maintenance therapy. This might be related to the certain protective property of СYP2E1 gene polymorphism. The AST level was increased after intensive therapy (to a smaller extent than for the patients with major C/C genotype) and remained on the same level at maintenance therapy. A study of GGT showed a gradual increase regardless of genotype. Conclusion. According to the data of the experiment, the status of hepatocytes in patients with tuberculosis at baseline and during treatment was different depending on the CYP2E1 genotype. The results of the experiment indicate that the CYP2E1 gene polymorphism has a certain protecting role. It reduces the level of drug metabolites and hepatotoxicity which causes mitochondrial dysfunction.

scholarly journals Increased monohexosylceramide levels in the serum of established rheumatoid arthritis patients

Rheumatology ◽  
2019 ◽  
Vol 59 (8) ◽  
pp. 2085-2089
Author(s):  
Gabriel Miltenberger-Miltenyi ◽  
Ana Rita Cruz-Machado ◽  
Jennifer Saville ◽  
Vasco A Conceição ◽  
Ângelo Calado ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Arthritis ◽  
Classification Criteria ◽  
Control Group ◽  
Established Rheumatoid Arthritis ◽  
Regression Analyses ◽  
Lipid Levels ◽  
Age And Gender ◽  
Patient Groups ◽  
And Gender

Abstract Objectives To identify serum sphingolipids that could act as candidate biomarkers in RA. Methods We performed lipidomic analyses in the serum of 82 participants: 19 established RA patients, 18 untreated early RA patients, 13 untreated early arthritis patients not fulfilling the classification criteria for RA, 12 established SpA patients and 20 controls. We compared the lipid levels from the different patient groups with the control group through multiple-regression analyses controlling for age at diagnosis, gender and medication (cDMARDs and corticoids). Results Established RA patients had significantly increased levels of sphingosine, monohexosylceramide and ceramide compared with controls, when controlling for age and gender. Monohexosylceramide levels remained significantly increased when additionally controlling for medication. On the contrary, SpA patients had significantly decreased levels of ceramide, in both analyses. Conclusion We observed a detectable increase in the levels of certain sphingolipids in the serum of established RA patients when compared with controls, in line with previous observations in the synovial fluid. Such findings provide further evidence that sphingolipids may play a key role in the pathophysiology of RA.

Gene Polymorphisms of Costimulatory Molecules: CTLA-4/CD28/ICOS Are Associated with B-Cell Chronic Lymphocytic Leukemia (B-CLL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2074-2074 ◽  
Author(s):  
Irena Frydecka ◽  
Katarzyna Suwalska ◽  
Edyta Pawlak ◽  
Lidia Karabon ◽  
Anna Tomkiewicz ◽  
...  
Keyword(s):  
T Cell ◽  
Gene Polymorphism ◽  
Costimulatory Molecules ◽  
N Gene ◽  
Control Group ◽  
Stepwise Logistic Regression ◽  
Polymorphism Analysis ◽  
Cell Functions ◽  
Increased Risk ◽  
Risk Of Cancer

Abstract There are strong evidences that altered immunological function entails an increased risk of cancer. Cytotoxic T-lymphocyte antigen 4 (CTLA-4), CD28, and Inducible co-stimulator (ICOS) are costimulatory molecules provide regulatory signals for T-cell activation. CD28 and ICOS potently enhance T-cell functions, while activation of T-cells is subsequently downregulated by CTLA-4. The abnormal expression of costimulatory molecules may be caused by polymorphisms of genes encoding these molecules. The extended study was undertaken to evaluate the association between the polymorphisms: CTLA-4+49A/G, CTLA-4-319C/T, CTLA-4(AT)n, CD28+17C/T, ICOS(GT)n and susceptibility to B-CLL in a Polish population. All together 124 B-CLL patients and 202 controls were studied. Single nucleotide polymorphisms were typed by minisequencing. The microsatellite polymorphisms were studied by PCR and fuorescence based technique. The distribution of -319T/C alleles and genotypes differed significantly between groups. The frequency of T allele and T phenotype was increased in patients with respect to controls (p=0.01, OR=1.74, 1.13∼95%CI∼2.68; p=0.01, OR =1.85, 1.13∼95%CI∼3.04, respectively). CTLA-4+49A/G and CTLA-4 (AT)n did not correlate with B-CLL. The analysis of the CD28+17C/T showed that the presence of C allele and C phenotype increased the OR of B-CLL by 1.97 and 2.07, respectively (p=0.002, 1.28∼95%CI ∼3.03; p=0.003, 1.27∼95%CI ∼3.38). For ICOS(GT)n gene polymorphism analysis we combined the alleles into 3 groups: (s)- short-alleles with 8 and 9 repeats, (m) -middle- with 10 and 11 and (l)- long- 12 and more repeats. The global distribution of alleles and genotypes was significantly different in patients and controls (p=0.00008 and p=0.00006, respectively). Individuals possessing (s) alleles were 2.75 times more prone to B-CLL than others (p=0.0000, OR=2.75, 1.67∼95%CI∼4.55), while carrying (l) alleles were protected to B-CLL (p=0.004, OR=0.47, 0.29∼95%CI∼0.79). The genotype (s)/(m) was overrepresented in patients (p=0.004, OR=2.29, 1.28∼95%CI∼2.09), but (l)/(l) individuals appeared more frequently in controls (p=0.002, OR=0.07, 0.00 ∼95%CI∼0.44). The haplotype association study of three polymorphic sites: CTLA-4-319C/T and CD28+17C/T and ICOS (s)/(m)/(l), which correlated with B-PBL in univariante analysis, showed that the distribution of haplotypes was different in cases and control, global p value was p= 3 ×108. Remarkable, the haplotypes T/C/(s) and T/T/(s) were presented only in B-CLL (p=0.0004, OR=62072, 3540∼95%CI∼1088238; p=0.00003, OR=3447, 203∼95%CI∼58334, respectively) while the haplotype C/T/(l) was significantly more frequent in control group as compared to B-CLL (p=0.000003, OR=0.3, 0.18∼95%CI∼0.51). B-CLL patients and controls polymorphic features for CTLA-4-319C/T, CD28IVS3+17C/T, ICOS (GT)n were subjected to multivariate forward stepwise logistic regression analysis. It appeared that C phenotype at CD28 T17int3C site increased twice risk of B-CLL (p=0.004, OR=2.09; 1.26∼95%CI∼3.48), while genotype (m)/(l) or (l)/(l) for ICOS gene protected from disease (p=0,0009, OR=0,41; 0,24∼95%CI∼0,69). We reported for the first time that the gene polymorphism of costimulatory molecules: CTLA-4/CD28/ICOS contribute to susceptibility to B-CLL.

scholarly journals Phenotypic manifestations of arterial hypertension according to polymorphism of vitamin D receptor gene

2021 ◽  
Vol 25 (1(97)) ◽  
pp. 89-94
Author(s):  
Yu. Repchuk ◽  
L. Sydorchuk
Keyword(s):  
Vitamin D ◽  
Gene Polymorphism ◽  
Arterial Hypertension ◽  
Vitamin D Receptor ◽  
Receptor Gene ◽  
Control Group ◽  
Vitamin D Receptor Gene ◽  
Vdr Gene ◽  
Qualitative Polymerase Chain Reaction ◽  
Vdr Gene Polymorphism

Objective. To determine the phenotypic manifestations of essential arterial hypertension (EAH) according to the vitamin D receptor gene polymorphism (VDR rs10735810, rs2228570).Material and methods. The case-control study involved 100 patients with EAH stage II, 1-3 degrees of blood pressure (BP), high and very high cardiovascular risk, 21% (21) men, 79% (79) women. The mean age of patients was 59.86 ± 6.22 y.o. The control group consisted of 60 healthy individuals, comparable in age and gender. To study the VDR gene polymorphism (rs10735810, rs2228570) performed a qualitative polymerase chain reaction in real-time. Results. Almost half of the patients with elevated normal BP (44.4%) and 34% of patients with EAH 2-3 d. there is concomitant diabetes mellitus (DM) type 2, while for EAH 1 d. it is only 19%. Obesity of 1-3 degrees was shown in 53% of patients with EAH: average EAH of 1 d. - 21%, among the EAH 2-3 d. - 25%. In the control group, 16% suffered from obesity. The distribution of VDR gene polymorphism genotypes according to the presence of DM showed that it was present in 35% of patients with AA-genotype, which is 1.6 times more often than in patients with GG-genotype (22%). Most smokers among patients with GG-genotype (26%), which is twice as common as those with AA- and AG-genotype (13% and 14%, respectively). Obesity of 1-3 degrees most often met among carriers of GG-genotype - 74%, and in the control group 14%. An elevated level of waist-hip ratio (WHR) among women with EAH was in 80% of the AA-genotype carriers, in the control group, all women had normal values. In 76% of the AG-genotype carriers and in 81% of the GG-genotype carriers, the WHR was increased by 2.3 and 2.8 times, respectively, that in the control group. Deviations of systolic and diastolic BP according to the VDR gene polymorphic variants have not been established.Conclusions. The AA-genotype is associated with DM 2 and with elevated WHR in women; GG-genotype - with elevated BMI, especially in men.

Prognostic Significance of IL-17,And IL-13 Along With IL-23R Gene Polymorphisms in Patients with Rheumatoid Arthritis in Iraqi Patients

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Ibrahim A Altamemi ◽  
Sally Alkhafaji
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Polymorphism ◽  
Disease Activity ◽  
Prognostic Value ◽  
Systemic Disease ◽  
Expression Level ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Das 28 ◽  
Control Serum

Rheumatoid arthritis is a systemic disease with very complex pathogenesis and feature of chronic synovitis. The biological effect of polymorphism on expression and functionality of IL-23R such as SNP can have functional and phenotypic consequences that make Il-23R as a risk factor for RA disease. Moreover recently there is a new trends to find out a new noninvasive prognostic biomarker for RA disease which may help in fallowing up disease. Thus the aim of present work is to find out if there prognostic value for IL-13 and IL-17in Rheumatoid arthritis through linking its expression level with disease activity score (DAS). Also To study if there is a role for IL-23R 11209026 gene polymorphism in disease susceptibility in Iraqi community by using healthy volunteer as a control group. To achieve this goal a Case control study has been conducted on 40 patient and 40 matched apparently health control. serum IL-17 and IL-13 concentration were measure by enzyme Linked immunosorbent assay According to manufactural instruction,measurement of disease activity was determine according to DAS 28 Score.RFLP PCR was used to study SNP of IL-23R gene polymorphism for patient and control group. Data were summarized, presented and analyzed using statistical package for social science (SPSS version 23). Result of present study found there was significant association between serum IL-17 and IL-13 level and RA disease (P<0, 001; and P<0, 001respectively). Moreover,there is significant positive correlation between expression level of both IL-17 and IL-13 with DAS28 (0.044,and 0.034 respectively). According to Receptor operating Curve both of IL-17 and IL-13 found to have high specificity and sensitivity 100%. Regarding to IL-23 R gene polymorphism,there was no significant correlation between rs11209026 gene polymorphism and susceptibility to rheumatoid arthritis patients in Iraqi community. Thus,present study showed that the concentrations of IL-13 and IL-17 significantly correlated with disease severity and DAS 28 which reflect their prognostic value in RA. Moreover,present study demonstrated that there was no significant association between Il-23R gene rs11209026 polymorphism and susceptibility to RA in Iraqi population.

P2X7 receptor gene polymorphism analysis in rheumatoid arthritis

2011 ◽  
Vol 38 (5) ◽  
pp. 389-396 ◽  
Author(s):  
A. Al-Shukaili ◽  
J. Al-Kaabi ◽  
B. Hassan ◽  
T. Al-Araimi ◽  
M. Al-Tobi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Polymorphism ◽  
P2x7 Receptor ◽  
Receptor Gene ◽  
Polymorphism Analysis ◽  
Receptor Gene Polymorphism

scholarly journals NO Level and Endothelial NO Synthase Gene Polymorphism (Glu298Asp) in the Patients with Coronary Artery Disease from the Turkish Population

2004 ◽  
Vol 36 (10) ◽  
pp. 661-666 ◽  
Author(s):  
Lale Afrasyap ◽  
Guler Ozturk
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Gene Polymorphism ◽  
Turkish Population ◽  
Control Group ◽  
Enos Gene ◽  
Nitric Oxide Level ◽  
Significant Difference ◽  
Artery Disease

Abstract Nitric oxide is synthesized from L-arginine by endothelial nitric oxide synthase encoded by eNOS gene. This study was performed to investigate the relationship between the serum nitric oxide level and eNOS gene polymorphism in the Turkish population with angiographically diagnosed coronary artery disease (63.47 ± 9.10 years old, n=250) and control subjects without any history and/or risk factors of coronary artery disease (60.71 ± 9.14 years old, n=150). Griess assay and PCR-RFLP analysis were used to measure the serum nitric oxide metabolites and genotypes, respectively. It was found that Glu/Glu, Glu/Asp and Asp/ Asp genotype frequencies of the eNOS were 49.3%, 41.3% and 9.3% respectively in the control group, and 45.6%, 41.2% and 13.2% in the patient group. Serum nitric oxide levels were (32.56 ± 17.26) μM in controls and (29.84 ± 11.88) μM in patients. Neither the frequencies of the Glu298Asp genotypes nor the serum nitric oxide levels showed a significant difference between the groups. There was also no correlation between serum nitric oxide levels and the frequencies of the eNOS genotypes. Result showed that the coronary artery disease of the Turkish population seemed to develop without any alterations in eNOS Glu298Asp genotype frequency and the serum nitric oxide level.

scholarly journals Relationships of oxidative stress and systemic inflammation markers depending on the degree and duration of hypertension

2016 ◽  
Vol 7 (2) ◽  
pp. 118-122
Author(s):  
T. Ashcheulova ◽  
N. Gerasimchuk
Keyword(s):  
Oxidative Stress ◽  
Arterial Hypertension ◽  
Systemic Inflammation ◽  
Control Group ◽  
C Reactive Protein ◽  
Multisystem Disease ◽  
Reactive Protein ◽  
And Gender ◽  
Relationship Of ◽  
Healthy Persons

Arterial hypertension (AH) is a heterogenic and multisystem disease. It has been suggested that oxidative stress (OS) and systemic non-specific inflammation may be involved in pathogenesis of cardiovascular pathology including AH. The aim of our study was to characterize the plasma C-reactive protein (CRP) level as a marker of systemic inflammation in relation to OS development (on the base of 8-isoprostane level assessment), depending on duration and degree of AH. We examined 117 persons, of which 102 patients from 30 to 65 years old (average age – 54.7 years) who had previously not been receiving regular antihypertensive therapy had I–III degrees of essential hypertension and 15 healthy persons (average age – 48.7 years). In 34 patients from this group the degree of OS activity was determined by 8-isoprostane level as the main marker of OS. The control group consisted of 10 healthy persons, by age and gender comparable with the study group. Determination of plasmatic CRP levels and the level of 8-isoprostane in the serum was performed by ELISA. The study established an increase of the plasmatic CRP levels in patients with hypertension, and a statistically significant increase of serum 8-isoprostane content in hypertensive patients compared to the control group. When assessing the relationship of 8-isoprostane and CRP content in patients with different degrees of hypertension we found that the strongest positive relationship between their levels was observed in the case of I degree hypertension. This may indicate the role of oxidative stress in the pathogenesis of hypertension as a damaging mechanism which contributes to the activation of immune mechanisms and further progression of the disease. Increased CRP and 8-isoprostane levels confirm the involvement of autoimmune mechanisms and oxidative stress in the pathogenesis of hypertension. The level of C-reactive protein is dependent on the duration of hypertension, while the 8-isoprostane levels – only on degree of hypertension. A raised level of C-reactive protein can be used as an independent marker of systemic inflammation in patients with arterial hypertension.

scholarly journals Rheumatoid Arthritis: Clinical-Laboratory and Ultrasound Parallels

2021 ◽  
Vol 11 (4) ◽  
pp. 271-276
Author(s):  
I. A. Krivotulova ◽  
T. V. Chernysheva
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Clinical Laboratory ◽  
Doppler Imaging ◽  
Comparative Characteristic ◽  
Tender Joint Count ◽  
Control Group ◽  
Interleukin 17 ◽  
Group I ◽  
Radiological Changes

Purpose. To establish the relationship of serum adiponectin and leptin with clinical data, serological parameters, disease activity, results of ultrasound examination of the musculoskeletal system and X-ray damage of joints in rheumatoid arthritis patients.Materials and methods. The article presents a comparative characteristic of adipokine levels among 64 women diagnosed with rheumatoid arthritis (group I) and 30 healthy women (group II). The dependence of adipokine levels on clinical, laboratory, ultrasound and radiological changes was revealed in patients with rheumatoid arthritis.Results. The concentration adiponectin level was significantly higher in rheumatoid arthritis patients compared to the control group (p <0.0001) and had significant correlations with radiological changes in the joints (r=0.40; p <0.001) and the intake duration of methotrexate (r=0.4; p <0.001) and glucocorticosteroids (r=0.3; p <0.05). The level of leptin in the blood serum of women with rheumatoid arthritis and healthy individuals was approximately the same. However, there were positive correlations between the level of leptin and of the tender joint count (r=0.5; p <0.0001), the levels of C-reactive protein (r=0.3; p <0.05) and interleukin-17 (r=0.3; p <0.05), the index Disease Activity Score 28 (r=0.4; p <0.001) and increased blood flow during Doppler imaging (r=0.4; p <0.001).Conclusion. Thus, patients with rheumatoid arthritis have a significant increase in the level of adiponectin compared to the health group, which is associated with pronounced destructive changes in the joints and the intake duration of methotrexate and glucocorticosteroids. However, a positive relationship between the indicators of disease activity and the presence of a Doppler signal is observed only in leptin.

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