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

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.

2018 ◽  
Vol 1 (4) ◽  
pp. 105
Author(s):  
Donglin Zhu ◽  
Yun Xi ◽  
Jieming Dong ◽  
Fanhua Huang ◽  
Changzhi Xu ◽  
...  

 Objective: To investigate the relationship between cytochrome P450 E1 (CYP2E1) gene polymorphisms and susceptibility to anti-tuberculosis drug-induced liver damage (ATDLI) in tuberculosis patients in the Chinese Han nationality. Methods: A retrospective analysis was performed on 360 patients with tuberculosis who had liver damage after tuberculosis treatment (case group) and 360 patients with tuberculosis who did not develop liver injury after treatment (control group). MassARRAY were used to detect CYP2E1 gene polymorphisms. Results: In a total of 8 tagged SNP loci selected, the rs8192773 locus failed to pass the test, and therefore, it is not included in subsequent analysis. At the remaining seven SNP sites, the difference in alleles was not statistically significant between the case group and the control group, suggesting that these sites may not be related to liver damage caused by anti-tuberculosis drugs. Three monomer domains were found in the seven tags SNP loci mentioned above. However, it was found that these haplotypes are not closely related to anti-tuberculosis drug-induced liver damage. Conclusion: The CYP2E1 gene polymorphism in the Chinese Han nationality is not related to the occurrence of anti-tuberculosis drug-induced liver injury.


2014 ◽  
Vol 3 ◽  
Author(s):  
Nurgul Sikhayeva ◽  
Zhannur Abilova ◽  
Ivan Shtefanov ◽  
Abai Makishev ◽  
Ainur Akilzhanova

Introduction. Breast cancer is the most common type of cancer among women. In Kazakhstan, breast cancer holds first place among causes of women death caused by cancer in the 45-55 year age group . Many studies have shown that the risk of acquiring breast cancer may be related to the level of calcium in the blood serum. One of the important regulators of calcium metabolism in the body is the parathyroid hormone. Single nucleotide polymorphisms in the gene encoding the parathyroid hormone (PTH) are associated with breast cancer development risk, and may modify the associative interaction between the levels of calcium intake and breast cancer. Experimental studies have shown that PTH gene has a carcinogenic effect. At least three studies showed a weak positive correlation between the risk of acquiring breast cancer and primary hyperparathyroidism, a state with high levels of PTH and often high levels of calcium. The aim of this investigation was to evaluate potential association between PTH gene polymorphism and breast cancer risk among Kazakhstani women.Methods. Female breast cancer patients (n = 429) and matched control women (n = 373) were recruited into a case – control study,. Genomic DNA was extracted from peripheral venous blood of study participants using Wizard® Genomic DNA Purification Kit (Promega, USA). Detection of PTH gene polymorphism (rs1459015) was done by means of the TaqMan® SNP Genotyping Assay of real-time PCR. Statistical analysis was conducted using SPSS 19.0.Results. PTH gene alleles were in Hardy–Weinberg equilibrium (p > 0.05). Distribution was 59% CC, 35% CT, 6% TT in the group with breast cancer and 50% CC, 43% CT, 6% TT in the control group. Total difference (between the group with breast cancer and the control group) in allele frequencies for PTH polymorphism was not significant (p > 0.05). No association was found between rs1459015 TT and breast cancer risk (OR = 1.039; 95%, CI 0.740 - 1.297; p = 0.893).Conclusion. We found no association between PTHrs1459015 polymorphism and breast cancer in our present study. Further studies are required to confirm our results and clarify role of PTH gene genotypes on breast cancer risk.


2019 ◽  
Vol 7 (20) ◽  
pp. 3387-3390
Author(s):  
Sukri Rahman ◽  
Eti Yerizel ◽  
Daan Khambri ◽  
Djong Hon Tjong

BACKGROUND: Various environmental factors have been suspected to be associated with the risk of developing Nasopharyngeal Carcinoma (NPC). Volatile nitrosamines found in salted fish are thought to be carcinogenic substances for NPC. Nitrosamines are activated by the CYP2E1 enzyme. Several studies investigated the relationship between polymorphism in the CYP2E1 gene and susceptibility to NPC, but the results obtained were inconsistent. AIM: This study was conducted to analyse the association of the CYP2E1 rs2031920 polymorphisms with the incidence of NPC in the Minangkabau ethnic group. METHODS: The subjects of this study were newly diagnosed NPC Minangkabau ethnic patients, while the controls were healthy people.  A total of 23 cases of NPC and 23 aged (± 3 years) and sex-matched controls participated in the study. The method used to identify these polymorphisms is PCR sequencing. RESULTS: On recent study, we found CYP2E1 rs2031920 gene polymorphism in both the NPC and control groups, in the NPC group there were 8.7% heterozygote mutants while in the control group there were 26.1% heterozygote mutants, and there were no homozygote mutants in the two groups, and statistically none a significant relationship between CYP2E1 gene polymorphism and the incidence of NPC, with p > 0.05. CONCLUSION: Our study reveals that there is no association of CYP2E1 gene polymorphism (rs2031920) with the incidence of nasopharyngeal carcinoma in the Minangkabau ethnic group.


2020 ◽  
Vol 9 (11) ◽  
pp. 3593
Author(s):  
Jolanta Masiak ◽  
Jolanta Chmielowiec ◽  
Krzysztof Chmielowiec ◽  
Anna Grzywacz

Background: Approximately 25–50% of people diagnosed with substance use disorder experience psychiatric disorders, and this percentage is even higher if subclinical psychopathological symptomatology is taken into consideration. ”Dual diagnosis” implies the comorbidity of two disorders (mental disorder and addiction), but in a clinical setting, numerous dual diagnoses involve multiple addictions (polysubstance use means the concurrent use of more than one psychoactive substance). Clinical observations and epidemiological studies showed that the use of stimulants in combination with other substances results in additional risks. Apart from the clinical significance of the specificity of stimulants used in combination with other substances, only non-exhaustive research on the specificity of this comorbidity has been performed to date. The aim of the study was to analyze polymorphisms of the genes (DRD4 VNTR in exon III Ex3, DRD2 rs1076560, rs1800498, rs1079597, rs6276, as well as in the PROM promoter region (rs1799732, ANKK1 Tag1A rs1800497, DAT) in a group of patients diagnosed with polysubstance use disorder, including addiction to stimulants, and the co-occurrence of specific mental disorders in a group of patients diagnosed with polysubstance use disorder, including addiction to stimulants, compared to the group of patients diagnosed with polysubstance use disorder. Methods: The study group consisted of 601 male volunteers with psychoactive substance dependence (n = 300) and non-dependent controls (n = 301). The genomic DNA was extracted from venous blood using standard procedures. Genotyping was conducted with the real-time PCR method. All computations were performed using STATISTICA 13. Results: Psychotic disorders were significantly more common in the group of males with polysubstance addiction, including addiction to stimulants, compared to the group of males with polysubstance addiction without addiction to stimulants. In our own research, different statistical significances were found in the frequency of the DRD4 Ex3 gene polymorphism: s/s was more common in the study group. Psychotic disorders were more common in people addicted to stimulants compared to people addicted to other substances. Conclusions: In our study, psychotic disorders occurred more frequently in the study group of patients with polysubstance addiction, including addiction to stimulants, compared to the control group of patients with polysubstance addiction, but with no addiction to stimulants. Different statistical significances were found in the frequency of the DRD4 Ex3 gene polymorphism: s/s was more common in the study group, while the l/l genotype was less frequent in the study group. In DRD2 PROM rs 1799732, the del allele occurred more often than the ins allele in the study group. In the DRD4 Ex3 gene polymorphism, the s allele was more common in the study group, and the l allele was less frequent. In the DRD4 Ex3 gene polymorphism for the s/s genotype, psychotic disorders and generalized anxiety were more common, while for the s/l and l/l genotype, they were less frequent. The DRD4 Ex3 polymorphism s alleles were more common for depressive episode, dysthymia, and psychotic disorders as well as generalized anxiety disorder. We see a clear genetic aspect here. However, we want to be careful and draw no definite conclusions.


2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Suhao Zhang ◽  
Enmin Ding ◽  
Haoyang Yin ◽  
Hengdong Zhang ◽  
Baoli Zhu

Long-term and continuous noise exposure can result in noise-induced hearing loss (NIHL), which is a worldwide problem resulting from the interaction of environmental and genetic factors. The ATP2B2 gene polymorphism can destroy cochlear hair cells and increase the risk of NIHL. A case-control study of 760 Chinese textile workers was conducted to investigate the relationship between ATP2B2 polymorphisms and NIHL susceptibility. Venous blood was collected and questionnaires were conducted by professional physicians. A case group and a control group which were typed by individuals’ pure-tone audiometry test results were set. Three polymorphism sites of ATP2B2 were genotyped by using the PCR technique. Analysis results revealed that the C allele of rs3209637 (95%CI=1.08–2.58, odds ratio OR=1.67, P=0.027) was a dangerous factor and could add to risks of NIHL in the Chinese employees. The data of stratified analysis revealed that individuals who are exposed to noise>95 dB with the rs3209637 C genotype have a higher susceptibility to NIHL (OR=1.34, 95%CI=1.07–1.68). Multifactor dimensionality reduction analysis revealed that the interaction between rs14154 and rs3209637 is linked to increased NIHL risk, and for the interaction among rs14154, smoking and drinking had the same function (OR=1.54 and 1.77, 95%CI=1.15–2.07, 1.33–2.37, and P=0.0037 and P<0.0001, respectively). Our results suggest that genetic polymorphism rs3209637 C within ATP2B2 is a risk factor for NIHL among Chinese employees and rs3209637 C could be a potential biomarker for NIHL patients.


Author(s):  
Kaitmazova N.K.

Purpose. To assess the efficacy and safety of the use of the immunomodulator polyoxidonium in preschool children with obstructive bronchitis. Material and methods. The study included 35 children, who, based on anamnesis, clinical, laboratory and instrumental examination methods, were diagnosed with obstructive bronchitis. The age of the examined children ranged from 3 to 6 years. The control group consisted of 11 healthy children. The material for obtaining immunological data in children was peripheral venous blood. In order to analyze immunological changes, the content of B-lymphocytes and immunoglobulins in the blood was studied. The investigated immunological data included 6 indicators. The content of immunoglobulins was determined by enzyme immunoassay according to the attached instructions. Statistical analysis of the revealed data was carried out using the Wilcoxon test using the Statistica 6.0 software. All children underwent dynamic laboratory examination and immunological parameters. The primary examination was carried out when the children were admitted to the hospital. Re-examination was carried out after the end of therapy. Group I (n = 19) included patients who received treatment according to the classical scheme. Group II children (n = 16) underwent complex therapy with an immunomodulator. The drug polyoxidonium was selected as the study drug. Results. The data obtained reflect the effectiveness of the use of the immunomodulator polyoxidonium in the complex therapy of obstructive bronchitis in children. Conclusion. Immunological data obtained during the initial examination reflect the development of dysfunction of the immune system in children. It was revealed that polyoxidonium has an immunotropic effect, this is verified by the optimization of the parameters of the humoral link of the immune system.


2021 ◽  
Vol 17 (3) ◽  
pp. 50-64
Author(s):  
I. S. Simutis ◽  
G. A. Boyarinov ◽  
M. Yu. Yuriev ◽  
D. S. Petrovsky ◽  
A. L. Kovalenko ◽  
...  

Aim of the study: to evaluate the effect of meglumine sodium succinate (MSS) on the efficacy of anticoagulant therapy in patients with severe COVID-19 infection complicated by bilateral community-acquired pneumonia.Materials and methods. Overall efficacy of treatment was analyzed in 12 patients hospitalized to ICU with the diagnosis of severe confirmed COVID-19 coronavirus infection (U07.1) complicated by bilateral multisegmental pneumonia. All patients received prophylactic anticoagulation with unfractionated heparin. The patients were divided into two groups: 7 of them received a multi-electrolyte solution containing MSS 5 ml/kg daily for the entire ICU stay (3-10 days) as a part of therapy; 5 patients received a similar volume of a conventional multi-electrolyte solution containing no metabolically active substrates and comprised a control group. Coagulation parameters were measured in arterial and venous blood of all patients at the following stages: 1) upon admission to the ICU; 2) 2-4 hours after the first dose of heparin; 3) 8-12 hours after the second dose of heparin; 4) 24 hours after the beginning of intensive therapy. On the 28th day of follow-up, mortality, duration of ICU stay, and incidence of thrombotic complications in the groups were evaluated. Nonparametric methods of statistical analysis were used to assess intragroup changes and intergroup differences.Results. The group of patients administered with MSS had significantly fewer thromboembolic events during 28 days of treatment and shorter ICU stay. These patients responded faster to anticoagulant therapy, which was suggested by more distinct changes in coagulation parameters, i.e. increased APTT, persisting viable thrombocyte population, reduced D-dimer and fibrinogen levels.Conclusion. The metabolic action of succinate possibly increases endothelial resistance to damaging factors and reduces its procoagulant activity. The hypothesis requires testing in a larger clinical study with a design including laboratory evaluation of the efficacy of varying doses of the studied drug as well as aiming at elucidation of the mechanisms of its effect on specific pro- and anticoagulation system components.


2012 ◽  
Vol 67 (5) ◽  
pp. 24-29
Author(s):  
V. N. Maximov ◽  
I. V. Kulikov ◽  
P. S. Orlov ◽  
V. V. Gafarov ◽  
S. K. Malyutina ◽  
...  

Aim: to evaluate association between genetic polymorphism (SNPs) and myocardial infarction (identified in recent GWAS) as markers of high risk of myocardial infarction (MI) in Siberian population. Patients were divided into 2 groups — MI patients and control group (ratio 1:2) and presented the sapmle of population of Novosibirsk (9400 patients, 45–69 years) within international project HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe). 200 patients with MI (129 men, 71 women) were included. Control group — individuals without MI (420) matched for age and sex. Genomic DNA was extracted from venous blood by phenol-chloroform extraction. Gene polymorphism of genes tested by real-time PCR according to protocol (probes TaqMan, Applied Biosystems, USA) with the use of ABI 7900HT. The following SNPs were studied: rs28711149, rs499818, rs619203, rs10757278 and rs1333049 (hr. 9), rs1376251, rs2549513, rs4804611, rs17465637. The association of SNP and MI was confirmed for 4 of 9 studied SNPs: rs1333049 (hr. 9), rs10757278 (hr. 9), rs499818 (hr. 6), rs619203 gene ROS1. Heart rate was associated with rs1333049 and rs10757278. Glucose level was associated with rs619203, rs28711149 and rs1376251. Total cholesterol and atherogenic index was associated with rs28711149. For the first time in Russian population the associations of GWAS with myocardial infarction SNPs was detected for rs619203, rs499818, rs1333049 and rs10757278. These genetic markers can be used for assessing the risk of myocardial infarction in Russian population. 


2006 ◽  
Vol 16 (Suppl 1) ◽  
pp. 448-451 ◽  
Author(s):  
M. Aban ◽  
M. Arslan ◽  
E. Tok ◽  
S. Tekes ◽  
T. Budak ◽  
...  

We investigated the association of CYP17 gene polymorphism with the risk of having endometrial cancer and a well-known precursor of it, endometrial hyperplasia. Group A (control group) consisted of 35 patients who had histologically proven normal endometrium. Group B and C consisted of 18 and 30 patients who had endometrial hyperplasia with and without atypia, respectively. Group D consisted of 57 patients who had endometrial cancer. Venous blood samples were collected from patients in groups, and polymerase chain reaction was performed to determine the CYP17 gene polymorphism. Significant increase of A1/A1 and a decrease of A1/A2 genotype frequencies have been determined in patients with endometrial cancer and with atypical endometrial hyperplasia. No significant differences were found between groups in the frequency of A2/A2 genotype. There was no significant difference between the groups in the meaning of allele distributions. CYP17 polymorphism had correlation with endometrial atypia and cancer. Related effects of different types of CYP17 gene variants on the progression of hyperplastic endometrial cells into carcinoma should be evaluated in further studies. Progress in this area would help us modulate preventive treatments used in those actual high–risk group patients.


2020 ◽  
Vol 4 (8) ◽  
pp. 471-474
Author(s):  
A.A. Chernova ◽  
◽  
S.Yu. Nikulina ◽  
Yu.A. Tolstokorova ◽  
◽  
...  

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.


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