Detoxification System Genes Research Articles

Analysis of the prevalence of detoxification system genes (<i>GSTM1</i>, <i>GSTT1</i>) with regard to ethnicity and environmental characteristics of the region of residence

Analysis of the prevalence of detoxification system genes (<i>GSTM1</i>, <i>GSTT1</i>) with regard to ethnicity and environmental characteristics of the region of residence

Prediction of uncontrolled course of bronchial asthma in children based on polymorphisms of genes of signaling molecules of the immune system and detoxification genes

Aim. To study the possibility of predicting the asthma control at various stages of the development of the disease, possibly on the basis of taking into account the genetic polymorphisms of Toll-like receptors, cytokines and detoxification system genes using the statistical method of learning neural networks.Materials and methods. We ex­amined 167 children with bronchial asthma. The degree of asthma control was determined, the following mutations were detected: TLR2-Arg753Glu, TLR4-Asp299Gly, TLR4-Ghr399Ile, TLR9-T1237C, TLR9-A2848G; IL4-C589T, IL6- C174G, IL10-G1082A, IL10-C592A, IL10-C819T, IL12B-A1188C, TNFa-G308A; GSTM, GSTT, GSTM/GSTT, GSTP1 Ile105Val, GSTP1 Ala114Val, by PCR. The STATISTICA Automated Neural Networks package was used to model neural networks.Results. The model is based on the MLP (15-9-3) multilayer perceptron architecture with a layer of 15 input neurons (by the number of analyzed variables), a hidden intermediate layer of 9 neurons and an output layer of 3 neurons by the number of values of the classified variable (control). The training algorithm was chosen by BFGS as the most adequate to the classification task. The error function is traditionally chosen as the sum of squared deviations. The activation function of output neurons is Softmax. The activation function of the intermediate layer is hyperbolic. The volume of the training sample was 88 sets. The volume of samples for testing and quality control of the model was 36 sets. The resulting model was able to predict 79.01% of the correct values of the target variable (the degree of asthma control).Conclusion. The application of the developed program makes it possible to predict the possibility of uncontrolled or partially controlled asthma at any stage of the disease, including preclinical and pre-nosological for groups with a high risk of asthma. This allows you to individually adjust the measures of secondary and even primary prevention of asthma within the personal­ization of therapeutic approaches.

The Effect of Bisphenol A on the IVF Outcomes Depending on the Polymorphism of the Detoxification System Genes.

The aim of the study was to analyze the relationship between the level of bisphenol A (BPA) in the blood and follicular fluid, the polymorphism of the detoxification system genes, and the outcomes of IVF cycles. The data of 300 infertile patients with fresh IVF-ET cycles were analyzed. The level of BPA in the blood and follicular fluid was determined by HPLC-MRM-MS/MS. Determination of genotypes of the detoxification system genes was carried out by the real-time PCR. The threshold level for determining BPA was 0.1 ng/mL. BPA was detected in 92.3% (277/300) blood and in 16.8% (49/292) follicular fluid (FF) samples. There was no correlation between BPA level in the blood and FF. In patients with the absence of the A allele of the SULT1A1 gene, BPA was detected in FF significantly more often (22.6% vs. 13.5%, p = 0.0341). There was an association (not statistically significant) between the level of BPA in the blood and the presence of the G allele of the GSTP1 gene (rs1695) and the C allele in the GSTP1 gene (rs1138272). Our data suggests the role of detoxification system genes in the metabolism of BPA in the human body. The influence of BPA and detoxification system genes on the IVF outcomes requires further research.

Polymorphism of the detoxification system genes and the main hystocompatibility complex HLA of Ii class in extremely premature newborns with congenital pneumonia

Objective. To study the polymorphism of HLA system genes of II class (DRB1, DQA1, DQB1) in extremely preterm infants with birth weight less than l500g with congenital pneumonia, and to determine the risk factors for the formation of this disease. Material and methods . The researchers carried out a comprehensive study of 103 newborns. Group I: children with clinical and laboratory signs of congenital pneumonia («=61), and Group II: children with respiratory distress syndrome and without congenital pneumonia («=42). Genomic DNA was isolated from lymphocytes of venous blood and buccal scraping epithelial cells. The HLA class II genes were analyzed using a classical polymerase chain reaction. Results . The group of children with congenital pneumonia revealed an increase in the frequency of alleles DRB1*04 and DRB1*15, together with DQB1 0302/0602 genotype, thus, these genes may have the predisposing effect to the development of this disease and may serve a molecular genetic predictor of this disease. The genotype of preterm newborns with congenital pneumonia included the DRB1*13, DQA1*0103, DQB1*0501, DRB1*13/13; DQA1*0101/0103; DQB1*0501/0602; GSTM1 +/+ GSTT1 +/+ DRB1*13 DQA1*0501 DQB1*0301, alleles less frequently, those alleles had a protective effect against the development of the lung tissue inflammation. We found no statistically significant differences in the frequency of low-functional alleles of the glutatitone-S-trans-ferase family genes (GSTM1 and GStTi). Conclusion. The results of the study can be used to personalize the treatment and diagnostic process for preterm infants.

The responses of Oncorhynchus mykiss coping with BDE-47 stress via PXR-mediated detoxification and Nrf2-mediated antioxidation system

The low brominated polybrominated diphenyl ether (PBDE) 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) is ubiquitous in the marine environment. To elucidate the stress response and possible mechanisms underlying BDE-47, the rainbow trout fish Oncorhynchus mykiss were selected and orally fed bait with BDE-47 concentrations of 50 ng/g and 500 ng/g. BDE-47 was found to be mainly accumulated in head kidney and caused lipid peroxidation after prolonged exposure. We studied the detoxification system genes pregnane X receptor (PXR) and downstream genes (cytochrome 3 A, CYP3 A; glutathione S-transferase, GST) and their corresponding enzyme activity and found that the above indicators in the treatment groups increased first and then decreased with time, while the 500 ng/g group showed more significant changes. Further, the antioxidant system gene expression levels of the NF-E2-related factor 2 (Nrf2) and downstream genes (superoxide dismutase, SOD; catalase, CAT) were found significantly up-regulated with concentration and time. The change in the enzyme activity of SOD and CAT showed the same tendency as that of indicators of detoxifying system. The results showed that BDE-47 can accumulated in head kidney and caused activate and fast increase of genes and enzymes of detoxification and antioxidant system in the short-term and then damage the response systems in longer times. After Pearson correlation analysis, the Integrated Biomarker Response (IBR) Index was established with malondialdehyde (MDA) content; PXR, Nrf2, SOD, and CAT gene expression; and CYP3 A, GST, and CAT enzymatic activity, which were significantly related to BDE-47 bioaccumulation (P < 0.5). The IBR value can indicate the ecotoxicological responses of the head kidney to different BDE-47 concentrations exposure, but the high activity of the antioxidant system might obscure the damage of the detoxification system.

POLYMORPHISM GENES OF DETOXIFICATION SYSTEM AND IMMUNEDEPENDENT MECHANISMS IN THE DEVELOPMENT OF GENITAL ENDOMETRIOSIS

Endometriosis is one of the most mysterious and unresolved problem in modern gynecology, taking the third place in the structure of gynecological diseases. In the genesis of endometriosis important role belongs to the metabolism genes, which are characterized by a large variability of molecular structure of DNA. It is proved that implantation of endometrial cells and their proliferation is provided, if a woman abuses humoral and cellular immunity.The aim of our study was to determine the role of polymorphisms genes of detoxification system and immunedependent mechanisms in the development of endometriosis.Material and methods. Surveyed 102 patients with internal genital endometriosis. The polymerase chain reaction investigated the frequency of polymorphic variants of genes GSTT1 and GSTM1. DNA extraction from peripheral blood was perfomed using the test system «AmpliSens». Determination of interleukins levels in serum was perfomed by the method monoparentale analysis using the test-ystems for IFA.Results of the study and their discussion. The results of the conducted researches have allowed to establish that genital endometriosis is significantly associated with deleting polymorphisms genes of detoxication system. Also, it was found that patients with internal endometriosis there is a hyperproduction of proinflammatory cytokines and tumor necrosis factor-α.Conclusions. Research factors of immune regulation, and gene deletions of the glutation-S-transferase is a promising for future research in terms of studying them as a potential marker for noninvasive diagnosis of endometriosis.

Response of detoxification system genes on Chironomus riparius aquatic larvae after antibacterial agent triclosan exposures

Triclosan (TCS) is an antimicrobial agent used in a range of personal care and consumer products and is commonly detected in aquatic ecosystems. In the present study, the effects of TCS at the molecular level on the detoxification system of Chironomus riparius aquatic larvae, a test organism widely used for the assessment of aquatic toxicology, were evaluated. The obtained results show that this xenobiotic was able to induce significant changes in transcripts from different cytochrome P450s and glutathione s-transferases genes, involved in phase I and phase II of detoxification system, respectively. In contrast, TCS did not affect the glutathione S-transferase enzyme activity nor the expression pattern of multidrug resistance-associated protein 1, which belongs to phase III of detoxification system. These results provide information about the effects of TCS on the detoxification mechanism of C. riparius and offers different biomarker genes that could be useful in ecotoxicological studies, risk assessment and bioremediation.

Важность и значение полиморфизма генов при преэклампсии

Was to conduct a systematic review of data on the relationship between polymorphisms genes of detoxification system and development of preeclampsia (РЕ). Рresents the main genes of detoxification system (GSTPI, GSTМI, GSTТI, GРХI, ЕРНХI, SOD-2, SOD-3, CYPIAL, MTHЕR, MTR) and their functions. Of interest is the possibility of calculating the individual risk of PE based on the results about the presence of a combination of different polymorphisms in the genotype of the female. Question about early diagnosis of РЕ remains controversial and not fully understood. It is necessary to conduct further in-depth, extended study of this problem. Key words: preeclampsia, oxidative stress, genes of the detoxification system.

Оцінка розповсюдження поліморфізму генів системи детоксикації у дітей з запальними захворюваннями кишковика

Оцінка розповсюдження поліморфізму генів системи детоксикації у дітей з запальними захворюваннями кишковика

Endometriosis as systemic genetic problem

Current data contributing to the origin and development of endometriosis (E) — sever common disease of reproductive age women are reviewed. Numerous theories and hypothesis as well as basic pathological mechanisms underlying E are briefly outlined. Whole gene-net and particular groups of candidate genes involved in E are presented. The later include genes of detoxification system, sex hormones and their receptors, cytokines gene, onco- suppressors the genes contributing to embryonic development of female reproductive organs and cell proliferation Major molecular genetic data imply epigenetic impact in the origin of disease which results from progressive disregulation of endometrium genome functions provoked by unfavorable combinations of candidate genes of some signaling pathways and defects in their expression due to abnormal methylation pattern. Histone modifications and the faults of miRNA content. In line with systemic genetic concept initial stages of E could be provoked by different genetic, epigenetic and even external factors which outcome is the same pathophysiological and pathomorphological damages clinically classified as E. Two feasible molecular genetic routs of E. are suggested. Both are relying on unscheduled expression of early embryonic genes such as WNT4, HOX10, HOX11, GALT provoking the changes in genetic program of endometriotic cells (metaplasia) and their subsequent progression as the lesions of ectopic endometrium

Expression of the Nrf2-system at the blood-CSF barrier is modulated by neonatal inflammation and hypoxia-ischemia

Transcription factor NF-E2-related factor-2 (Nrf2) is a key regulator of endogenous anti-oxidant systems shown to play a neuroprotective role in the adult by preserving blood-brain barrier function. The choroid plexus, site for the blood-CSF barrier, has been suggested to be particularly important in maintaining brain barrier function in development. We investigated the expression of Nrf2- and detoxification-system genes in choroid plexus following systemic LPS injections, unilateral cerebral hypoxia-ischemia (HI) as well as the combination of LPS and HI (LPS/HI). Plexuses were collected at different time points after LPS, HI and LPS/HI in 9-day old mice. mRNA levels of Nrf2 and many of its target genes were analyzed by quantitative PCR. Cell death was analyzed by caspase-3 immunostaining and TUNEL. LPS caused down-regulation of the Nrf2-system genes while HI increased expression at earlier time points. LPS exposure prior to HI prevented many of the HI-induced gene increases. None of the insults resulted in any apparent cell death to choroidal epithelium. These data imply that the function of the inducible anti-oxidant system in the choroid plexus is down-regulated by inflammation, even if choroid cells are not structurally damaged. Further, LPS prevented the endogenous antioxidant response following HI, suggesting the possibility that the choroid plexus may be at risk if LPS is united with an insult that increases oxidative stress such as hypoxia-ischemia.

Herpesvirus type 7 infection may play an important role in individuals with a genetic profile of susceptibility to Graves' disease

An inherited profile of genes related to the response to aggressive environmental factors such as viruses and chemicals may be related to an increased susceptibility to Graves' disease (GD). This prospective case-control study was designed to examine the relationship between human herpesviruses (HHV) infection, determined by circulating DNA; tumour protein p53 (TP53) apoptotic ability; and detoxification system genes, and GD. We studied 280 confirmed GD patients paired to 284 controls with respect to environmental exposure. Exclusion criteria included medications that could interfere with thyroid function evaluation and a recent history of viral and bacterial infections. A stepwise regression analysis adjusted for age, gender, and ethnicity established the inheritance of glutathione S-transferase pi 1 (GSTP1) (odds ratio (OR)=3.423; 95% confidence interval (CI)=2.120-5.527; P<0.001) and cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) variants (OR=1.649; 95% CI=1.012-2.686; P=0.0445) as significant risk factors for the disease. HHV-7 infection was much more common in GD patients (64.64%) than in controls (38.73%; chi(2), P<0.0001), and it increased the risk for GD more than three times (OR=3.133; 95% CI=1.959-5.011; P<0.0001). The inheritance of less efficient Pro/Pro TP53 gene variants significantly increased the risk of GD development (OR=5.196; 95% CI=2.112-12.783; P<0.0001) and also favored HHV-7 infection (OR=2.835; 95% CI=1.100-7.310; P=0.0275). In addition, 72TP53 variants augmented the risk of GD relapse (OR=1.860; 95% CI=1.015-3.410; P=0.0446). We suggest that an inherited genetic profile involving TP53 may favor HHV-7 infection and maintenance, which, in turn, may initiate and perpetuate GD autoimmune process.

Possible involvement of arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 genes in the development of endometriosis

Wide inter-individual variation of expression of compound metabolic enzymes is determined by polymorphism and may predispose the development of diseases provoked by environmental factors. The combined analysis of phase II detoxification system genes: arylamine N-acetyltransferase 2 (NAT2), and glutathione S-transferases (GST) M1 and T1 was carried out in patients with minimal/mild (group I; n = 36) and moderate/severe endometriosis (group II; n = 29) and controls (n = 72) of French origin, using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The results show a significant difference between patients and controls with regard to NAT2 gene polymorphism (P < 0.05). This is mainly due to the high percentage of slow acetylator genotypes (SA) in patients compared with controls (60.0 versus 38.9%; P < 0.02) with a distinct preponderance in subjects with minimal/mild endometriosis (69.4%, P < 0.005) where there is a significantly elevated frequency of slow allele S1 (NAT2*5) (P = 0.05). Significantly increased proportions of GSTM1-deficient genotypes were found in both groups of patients, in comparison with the controls (75.0 and 79.3% versus 45.8%; P < 0. 0001). A preponderance of GSTT1-negative subjects among patients was also detected, but did not appear significant. We suggest the involvement of both NAT2 and GSTM1 detoxification system genes in the pathogenesis of endometriosis and the possible impact of NAT2 gene polymorphism in the development of different forms of this disease.