GSTP1 Gene Polymorphisms Research Articles

Are changes in olanzapine-induced liver enzyme levels associated with GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms?

Olanzapine treatment sometimes produces transient liver biochemistry abnormalities, and such drug-induced liver injuries are mainly monitored by measuring blood levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), whereas alpha-glutathione-S-transferase (α-GST) is not routinely measured in clinics, even though it can serve as an earlier and more specific biomarker of liver damage. Susceptibility to drug-induced liver injury can much depend on the gene polymorphisms regulating the activity of DNA detoxification and repair enzymes. The aim of this study was to evaluate which of the three liver enzymes - α-GST, ALT, and AST - is the most sensitive biomarker of olanzapine-induced liver injury and how their blood levels are affected by the GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms in 30 olanzapine-treated patients. Contrary to our hypothesis, the increase in serum α-GST levels was not significantly greater than that of the transaminases. ALT turned out to be an earlier biomarker of liver injury than the other two enzymes. No significant association was found between gene polymorphisms and liver enzyme levels, save for GSTP1 Ile/Val + Val/Val and ALT, which points to this genotype as a risk factor for drug-induced liver injury. Future studies might help to identify the underlying mechanisms of transient liver enzyme increase associated with this genotype.

Асоціація поліморфізмів генів GSTP1(A313G), MTHFR (С677T) та IL-10 (C819T) із ризиком виникнення гліобластоми

гліобластома одна з найбільш поширених злоякісних пухлин головного мозку з вкрай низькою виживаністю. Незважаючи на досягнення у вивченні молекулярного патогенезу та біології пухлин мозку, причини виникнення гліобластоми залишаються нез’ясованими. Дослідження останніх років вказують, що зміни у генах, які беруть участь у проліферації, диференціації та апоптозі клітин, можуть впливати на ризик виникнення онкологічних захворювань. Тож метою роботи було дослідити поліморфізми генів GSTP1(A313G), MTHFR (С677Т) та IL-10 (C819T) у хворих на гліобластому та проаналізувати їх зв’язок із ризиком розвитку цієї патології. Біологічним матеріалом для аналізу поліморфізмів генів GSTP1, MTHFR та IL-10 слугувала периферична кров хворих на гліобластому та практично здорових людей. Дослідження поліморфізмів генів проводилось за допомогою методу алель-специфічної ПЛР із використанням власних пар детекторів TaqMan MGB на основі флуоресцентних барвників, що призначені для виявлення однонуклеотидних замін. Встановлено, що частота мутантного алеля G гена GSTP1 у хворих становила 53,6% проти 32% у групі практично здорових людей. Розподіл генотипів гена GSTP1 у групі хворих відповідав закону генетичної рівноваги Харді-Вайнберга та статистично відрізнялась від показника у групі практично здорових людей і становив 0,538 проти 0,320 (χ2 = 13,10, р = 0,003). Визначено, що ризик виникнення гліобластоми є в 4,88 разів вищим у осіб, що є гомозиготними носіями мутантного алелю гена GSTP1 (генотип G313G) у порівнянні з іншими поліморфними варіантами. В результаті наших досліджень, було встановлено, що частота мутантного алеля С гена IL-10 у хворих становила 48,8%, що значно перевищує відповідний показник у групі практично здорових людей – 25%. Встановлено, що розподіл генотипів гена IL-10 у групі хворих відповідав закону генетичної рівноваги Харді-Вайнберга, частота мутантного алеля С гена IL-10 статистично відрізнялась від показника у групі практично здорових людей та становила 0,488 проти 0,250 (χ2 = 18,32, р = 0,00002). Встановлено, що існує асоціація між поліморфізмом гена IL-10 (C819T) та ризиком виникнення гліобластоми, у гомозиготних носіїв із генотипом Т819Т, ризик захворіти збільшується у 6,40 рази. Також нами було встановлено, що частота мутантного алелю Т гена MTHFR у хворих становила 35,0% проти 28,1% у групі практично здорових людей. Розподіл генотипів гена MTHFR у групі хворих відповідав закону генетичної рівноваги Харді-Вайнберга, а розподіл частот поліморфних варіантів ген показав відсутність статистично достовірних відмінностей між групою хворих та групою практично здорових людей (χ2 = 1,43 р = 0,23). Не було встановлено асоціації між поліморфізмом гена MTHFR (С677Т) і ризиком виникнення гліобластоми.

Association of glutathione-S-transferase gene polymorphisms with various disease (review of foreign studies)

Introduction. This review is devoted to the association of GSTM1, GSTT1, GSTP1 gene polymorphisms with various diseases in foreign literature sources.
 Material and methods. For this article, we used data published in foreign literature over the past 11 years. medline was extensively searched for eligible studies using the Pubmed search engine, and 30 studies were eventually selected for inclusion in this review.
 Results. This review showed that researchers all over the world have repeatedly tried to evaluate the relationship between GST polymorphisms and various diseases, but in some cases received conflicting results. At the same time, many studies have found an association of pathologies with both single GST gene polymorphisms and combined polymorphic variants, which indicates a complex effect of antioxidant system genes.
 Limitation of the study. The limitation of this review is the lack of domestic literary sources.
 Conclusion. Further research of functional polymorphisms of the GST family genes are needed to develop effective systems for the diagnosis, prevention, and treatment of diseases.

Glutathione S-Transferase P1 Genetic Variant's Influence on the HbA1c Level in Type Two Diabetic Patients.

GST (glutathione S-transferases) are capable of influencing glucose homeostasis, probably through regulation of the response to oxidant stress. The aim of our study was to investigate the relationship between GSTP1 gene polymorphism and glycated hemoglobin (HbA1c) levels in type two diabetic (T2D) patients. A total of 307 T2D patients were included. Analysis of the GSTP1 gene polymorphism (rs1695) was conducted using the TaqMan qPCR method endpoint genotyping. HbA1c was determined using a COBAS 6000 autoanalyzer. A univariable linear regression and multivariable linear regression model were used to investigate the association between mean HbA1c level and GSTP1 gene polymorphism, age at T2D diagnosis, T2D duration, therapy with insulin, gender, BMI, smoking status. GSTP1 Val/Val genotype, age at T2D diagnosis, T2D duration and therapy with insulin were statistically significant contributors to HbA1c levels (p < 0.05). Multivariable regression analysis revealed that GSTP1 (Val/Val vs. Ile/Ile) was associated with higher HbA1c even after adjustment for variables that showed a statistically significant relationship with HbA1c in univariable analyses (p = 0.024). The results suggest that GSTP polymorphism may be one of the risk factors for higher HbA1c in T2D patients. Our study is limited by the relatively small sample size, cross-sectional design, and lack of inclusion of other oxidative stress-related genetic variants.

Immunological and genetic predictors of breast cancer

Aim. To investigate the associations of idiotypic IgA antibodies against benzo[a]pyrene, estradiol and progesterone (IgA1 -Bp, IgA1 -E2, and IgA1 - Pg) with the corresponding anti-idiotypic IgG antibodies to estradiol and progesterone (IgG2 -E2 and IgG2 -Pg) and with gene polymorphisms of CYP1A1, CYP1A2, CYP1B1, CYP17A1, CYP19A1, GSTM1, GSTT1, and GSTP1 in patients with stage 1 breast cancer. Materials and Methods. Idiotypic and anti-idiotypic antibodies in the serum of 240 healthy women and 505 patients with stage 1 breast cancer were measured by enzyme-linked immunosorbent assay. Prevalence of CYP1A1 (rs4646903), CYP1A2 (rs762551), CYP1B1 (rs1056836), CYP19A1 (rs2470152), GSTM1(del), GSTT1(del), and GSTP1 (rs1695) polymorphisms in 530 healthy women and 694 patients with stage 1 breast cancer were determined by real-time polymerase chain reaction.Results. Low personal IgA1 -Bp/IgA1 -Pg < 1 and IgA1 -E2/IgA1 -Pg < 1 ratios in combination with low IgG2 -E2 ≤ 4 and high IgG2 -Pg > 2 levels were found in 20.6% of healthy women and in 4.5% of breast cancer patients (p < 0.0001; OR = 0.2). Low IgA1 -Bp/IgA1 -Pg and high IgA1 -E2/IgA1 -Pg ratios in combination with low IgG2 -E2 and high IgG2 - Pg levels were revealed in 7.4% of healthy women and 2.8% of breast cancer patients (p = 0.009; OR = 0.4). These two variants were integrated and marked as protective immunological phenotype. High IgA1 - Bp/IgA1 -Pg and high IgA1 -E2/IgA1 -Pg ratios combined with high IgG2 -Pg and high or low IgG2 -E2 levels were found in 17.2% of healthy women and27.2% of breast cancer patients (p = 0.006; OR = 1.8) and in 6.4% of healthy women and in 18.3% of breast cancer patients (p < 0.0001; OR = 3.3), correspondingly. These two variants were integrated and marked as pro-carcinogenic immunological phenotype. These associations were found only with estrogen receptor-positive (ER+) breast cancer. GSTP1 (rs1695) gene polymorphism was associated exclusively with estrogen receptor-negative (ER-) breast cancer (p = 0.004; OR = 1.56). No interrelations be tween immunological phenotypes and studied polymorphisms of CYP and GST genes have been found.Conclusion. Pro-carcinogenic immunological phenotype and rs1695 gene polymorphism within the GSTP1 gene were independent predictors of ER+ and ER- breast cancer correspondingly.

Молекулярно-генетические аспекты риска здоровью во взаимосвязи с неблагоприятными условиями окружающей среды и питанием (систематический обзор)

At present, it is vital to examine adverse effects produced on gene expression by negative environmental factors and nutrients. In this study, our aim was to generalize data available in literature on an association between health risks and polymorphisms of genes that participated in xenobiotic detoxification and allergic status, food intolerance included, in adults and children. We also considered influence exerted by various components in diets on gene expression. Available research data indicate that GSTP1 and SOD gene polymorphisms have their effects on a decline in detoxification and antioxidant functions and early development of allergic, occupational and oncological diseases under exposure to harmful chemicals. Micronutrients in diets that can protect from adverse effects produced by chemicals can act not only as substrates but also as detoxification enzyme inducers. Great quantities of biologically active compounds in the Mediterranean diet are assumed to be able to modulate functional activity of certain genes. Such nutrients as polyphenols, flavonoids, catechins, glucosinolates, anthocyanins, stilbenes, carotinoids, polyamines, spermidine and spermine produce anti-genotoxic and anti-carcinogenic effects. Use of combined nutrigenetic and phenotypic data seems a promising trend in effective modeling of a healthy diet. The research data outlined in this review indicate there is solid evidence that health risks can depend on a genotype, phenotype and quality of the environment. These risks also differ depending on a diet. Modeling a healthy diet based on available knowledge on nutritional genetic and nutritional genomics is a promising trend within non-carcinogenic health risk management, including risks of oncological diseases caused by exposure to adverse environmental factors.

Molecular and genetic aspects of health risks and their association with adverse environmental conditions and diets (systemic review)

At present, it is vital to examine adverse effects produced on gene expression by negative environmental factors and nutrients. In this study, our aim was to generalize data available in literature on an association between health risks and polymorphisms of genes that participated in xenobiotic detoxification and allergic status, food intolerance included, in adults and children. We also considered influence exerted by various components in diets on gene expression. Available research data indicate that GSTP1 and SOD gene polymorphisms have their effects on a decline in detoxification and antioxidant functions and early development of allergic, occupational and oncological diseases under exposure to harmful chemicals. Micronutrients in diets that can protect from adverse effects produced by chemicals can act not only as substrates but also as detoxification enzyme inducers. Great quantities of biologically active compounds in the Mediterranean diet are assumed to be able to modulate functional activity of certain genes. Such nutrients as polyphenols, flavonoids, catechins, glucosinolates, anthocyanins, stilbenes, carotinoids, polyamines, spermidine and spermine produce anti-genotoxic and anti-carcinogenic effects. Use of combined nutrigenetic and phenotypic data seems a promising trend in effective modeling of a healthy diet. The research data outlined in this review indicate there is solid evidence that health risks can depend on a genotype, phenotype and quality of the environment. These risks also differ depending on a diet. Modeling a healthy diet based on available knowledge on nutritional genetic and nutritional genomics is a promising trend within non-carcinogenic health risk management, including risks of oncological diseases caused by exposure to adverse environmental factors.

The Impact of CYP3A5, CYP1A1, GSTM1, GSTT1, GSTP1 and TPMT Gene Polymorphisms on the Risk of Chronic Myeloid Leukemia

Polymorphisms in the genes encoding drug metabolising enzymes (DME) cause inter-individual variations in metabolising exogenous and endogenous substances, which has been related to the risk of various diseases. The present study was conducted to investigate the association of CYP1A1, GSTM1, GSTT1, GSTP1 and CYP3A5 and TPMT gene polymorphisms with susceptibility to chronic myeloid leukemia (CML). 89 samples of CML patients and 135 control samples were included in this study. Genotyping of CYP1A1, GSTM1, GSTT1, GSTP1 and CYP3A5 and TPMT gene polymorphisms was performed by a Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP). The frequency of GSTM1 null genotype was found to be significantly higher among chronic myeloid leukemia (CML) patients vs controls (39% vs 18.5%, respectively) with a 2.85-fold increased risk for CML. The frequency of GSTT1 null was found to be significantly lower in CML patients vs controls (26% vs 40.7%). Under the dominant inheritance model, GSTP1 gene polymorphism was significantly associated with reduced risk of CML. Moreover, CYP3A5 * 6 and TPMT * 2 alleles were absent among CML patients and the control group. GSTM1 null genotype was found to be associated with an increased risk of CML whereas TPMT * 2 and CYP3A5 * 6 alleles were absent in the population of Punjab.

GSTP1 rs1695 polymorphism, oxidative stress markers, and antioxidants in coronary artery disease

Oxidative damage is among the essential factors in the progression of cardiovascular disease. Objectives: This study aims to evaluate the molecular role of GST genotypic polymorphism involved in the development of CAD. This study also aimed to compare the levels of oxidative stress and antioxidant markers in subjects with CAD with age and sex-matched controls. Result: There was no significant difference in allele frequency (p= 0.85) or genotype frequency (p= 0.85) between the examined case and control groups. Compared to healthy controls, F2-Isoprostanes and MDA levels were considerably elevated in individuals with coronary artery disease. CAD patients' GST, SOD, Vitamine E, and Vitamin C levels were considerably lower than in normal control subjects. Conclusion: This study observed that oxidative stress markers were significantly higher, whereas, in CAD patients, enzymatic and nonenzymatic-enzymatic antioxidants were significantly lower. This study could not find a good connection between GSTP1 gene polymorphism rs1695 and coronary artery disease.

Influence of GSTP-1 Polymorphism on the Prognosis of Patients with High-Grade Glioma Who Received Temozolomide Plus Radiotherapy Adjuvant Treatment.

BackgroundGlutathione S-Transferase P 1 (GSTP-1) gene plays an important physiological role in the body. The present study was conducted to identify the clinical implication of GSTP-1 gene polymorphism on the prognosis of patients with high-grade glioma (HGG) who received temozolomide plus radiotherapy adjuvant treatment.MethodsThis study recruited a total of 186 patients with HGG who were treated with temozolomide plus radiotherapy adjuvant regimen (retrospectively). Baseline clinical characteristics were obtained and the prognostic data of the patients were collected. Peripheral blood specimen of patients was preserved for genotyping of GSTP-1 polymorphism during hospitalization. Correlation analysis was carried out accordingly. Additionally, fresh peripheral blood specimens that were available for mRNA expression analysis were collected for the mRNA expression analysis.ResultsThe median progression-free survival (PFS) and overall survival (OS) of the 186 patients with HGG who received temozolomide plus radiotherapy regimen was 8.5 months (95% CI: 5.95–11.05) and 15.5 months (95% CI: 11.49–19.51), respectively. The prevalence of 313A>G among 186 patients with glioma was AA genotype: 126 cases (67.7%), AG genotype: 54 cases (29.1%), GG genotype: 6 cases (3.2%), minor allele frequency of 313A>G was 0.18. Association analysis suggested that the median PFS of patients with AA and AG/GG genotypes was 11.2 and 5.0 months, respectively (χ2=11.17, P=0.001). Furthermore, the median OS of patients with AA and AG/GG genotypes was 18.9 and 10.5 months, respectively (χ2=12.684, P<0.001). Besides, when adjusted for PFS in multivariate Cox regression analysis, AG/GG genotype was an independent factor for PFS (HR=0.48, P=0.006). The mRNA expression results indicated that mRNA expression of GSTP-1 in patients with AG/GG genotypes of 313A>G was significantly higher than that of patients with AA genotype (P<0.001).ConclusionGSTP-1 polymorphism 313A>G might be used as a potential biomarker to predict the prognosis of patients with HGG who received temozolomide plus radiotherapy adjuvant treatment.

Allele and genotype frequencies of CYP3A4, CYP3A5, CYP3A7, and GSTP1 gene polymorphisms among mainland Tibetan, Mongolian, Uyghur, and Han Chinese populations.

Over 50% prescribed drugs are metabolised by cytochrome P450 3A (CYP3A) and glutathione S-transferase pi (GSTP1) adds a glutathione to the oxidative products by CYP3A, which increases the hydrophilic property of metabolites and facilitates the excretion. Single nucleotide polymorphisms (SNPs) of CYP3A and GSTP1show a diverse allele and genotype frequencies distribution among the world populations. The present study aimed to investigate the genotype and allele frequency distribution patterns of CYP3A4, CYP3A5, CYP3A7 and GSTP1 polymorphisms among healthy participants in mainland Tibetan, Mongolian, Uyghur, and Han Chinese populations. Blood samples were collected from 842 unrelated healthy subjects (323Tibetan, 134Mongolian, 162 Uyghur, and 223 Han) for genotyping analysis. Variant allele frequencies of CYP3A4 rs2242480, CYP3A5 rs776746, CYP3A7 rs2257401, and GSTP1 Ile105Val were observed in Han (0.253, 0.686, 0.312 and 0.188), Tibetan (0.186, 0.819, 0.192 and 0.173), Mongolian (0.198, 0.784, 0.228 and 0.235) and Uyghur (0.179, 0.858, 0.182 and 0.250) respectively. The allele frequency of CYP3A7*1C in Uyghur (0.019) was higher than that in Tibetan (0.002, p<0.01). There was a strong linkage disequilibrium between CYP3A4 rs2242480, CYP3A5 rs776746, and CYP3A7 rs2257401 among the four ethnic groups. The results might be useful for the precise medication in the Chinese populations.

The Cumulative Effect of Gene-Gene Interactions Between GSTM1, CHRNA3, CHRNA5 and SOD3 Gene Polymorphisms Combined with Smoking on COPD Risk.

BackgroundChronic obstructive pulmonary disease (COPD) is a multifactorial disorder which is affected by external and internal risk factors. People with no external risk factors may be significantly affected and develop pulmonary disease. The study aimed to define gene–gene and gene–environmental effects on COPD.MethodsA case control study involved 181 COPD patients and 292 healthy individuals, with peripheral blood sampling and adequate questionnaires. Genotyping was done with various types of PCR design for GSTM1 (null del), GSTT1 (null del), EPHX1 (rs2234922 and rs1051740), GSTP1 (rs1695 and rs1138272), CHRNA3 (rs1051730 and rs12914385), CHRNA5 (rs16969968 and rs17486278), and SOD3 (rs1799895 and rs699473) gene polymorphisms. Gene–gene and gene–environmental interactions were investigated using multidimensional regression analysis.ResultsFrequency of risk alleles of rs1051730 (p = 0.001), rs16969968 (p <0.001), and rs1799895 (p <0.001) polymorphisms were significant in univariate analysis. For gene–gene interaction, GSTM1 null, rs1051730, rs16969968, and rs1799895 polymorphisms independently contributed to risk of COPD and any combinations of the risk genotypes have a higher risk of disease. A cumulative effect of the four risk polymorphisms increased the risk of COPD for the smoking index (cOR = 13.6, p <0.001), cigarettes per day (cOR = 32.08, p <0.01), nicotine dependence (cOR = 12.0, p <0.01), and smoking status (cOR = 17.02, p <0.01) for gene–environmental interaction.ConclusionSeveral pivotal genes showed distinct effects for COPD, and some synergistic effects affected the disease progression. The development of COPD was synergistically increased with gene–gene and gene–environmental risk factors.

Ассоциация полиморфизмов гена глутатион-S-трансферазы с риском развития мужского бесплодия в Московском регионе

About 30% of male infertility is associated with genetic abnormalities. Genetic polymorphisms increase the level of individual susceptibility to adverse environmental factors and affect human reproductive function. Aim To study associations of glutathione S-transferase GSTP1(Ile/Val) gene polymorphisms (A313G; rs1695) with the risk of pathospermia in men of the Moscow region. Materials and methods We examined 138 men in the Moscow region (n=70 - proven pathospermia, n=68 - fertile men). We obtained genomic DNA from blood leukocytes and studied the gene polymorphisms of glutathione-S-transferase GSTP1 (Ile/Val) (A313G; rs1695) in real time. Results In the analysis of the distribution frequencies of polymorphisms GSTP1 (Ile/Val) (A>G rs1695), we revealed the predominance of the AA genotype in fertile men and the predominance of the GG genotype (homozygous minor allele) in men with pathospermia. However, we found no significant difference in these parameters between the compared groups of patients (p=0.344). For GSTP1 (Ile/Val) polymorphism (A313G, rs1695), significant differences in the distribution of genotype frequencies in the subgroup of men with teratospermia (2=7.00; p=0.03) were revealed. The frequency of allele G in the subgroup of men with teratospermia is statistically significantly different from the frequencies of alleles in the control group: 52% versus 30% (2=10,004; p=0.0015). In subgroups of men with azoospermia and asthenospermia, we did not find significant differences in the distribution of genotypes of GSTP1 polymorphism (rs1695) (p>0.05). Discussion Glutathione-S-transferase (GSTP1) is a multifunctional protein that protects sperm cells from the damaging effects of reactive oxygen species and xenobiotics. The Association of GSTP1 polymorphism (Ile/Val) (A313G, rs1695) with teratospermia explains the main stages of the pathogenesis of male infertility in this category of patients. Conclusion Gene polymorphism GSTP1 (A313G, rs1695) can be considered a genetic marker of susceptibility to pathospermia in men.

The Relationship Between GSTT1, GSTM1, GSTO1, GSTP1 and MTHFR Gene Polymorphisms and DNA Damage of BRCA1 and BRCA2 Genes in Arsenic-Exposed Workers.

To investigate the associations between genetic polymorphisms of GSTT1, GSTM1, GSTO1, GSTP1 and MTHFR genes and the DNA damage levels of BRCA1 and BRCA2 genes. Peripheral blood samples were used to measure DNA damage levels and genetic polymorphisms, and urine samples were collected to analyze arsenic metabolites in 79 arsenic-exposed workers and 24 non-arsenic-exposed workers. The BRCA1 and BRCA2 damage levels in exposure group were significantly higher than that in control group. Significant associations were detected between GSTT1 and GSTO1 polymorphisms and DNA damage levels of BRCA1 and BRCA2 genes in subjects (P < 0.05). Our findings suggest that the DNA damage levels of BRCA1 and BRCA2 genes may modulate by genetic variations of GSTT1 and GSTO1 when individuals are exposed to carcinogens, such as arsenic.

Parameters of the glutathione system and thioredoxin in blood plasma and ascites and GSTP1 Ile105Val gene polymorphism as factors of resistance to platinum-containing chemotherapy in ovarian cancer patients

Background . Chemotherapy is one of the main types of treatment in ovarian cancer. Standard first-line treatment includes platinum drugs. Every fifth patient develops chemoresistance after platinum-containing first line therapy. Glutathione detoxification systems play an important role in platinum drugs utilization. Purpose. To assess the redox status of blood plasma and ascitic fluid in ovarian cancer patients before and after neoadjuvant platinum-containing chemotherapy (NACT). Materials and methods . We determined the activity of the glutathione system and thioredoxin levels in blood plasma before and after NACT and in the ascitic fluid before NACT, and the presence of GSTP1 gene polymorphism (Ile105Val (rs1695), Ala114Val (rs1138272) in 30 III–IV FIGO stage ovarian cancer patients. Patients were divided into 3 groups: NR – no relapse in 2 years after last chemotherapy course; R1 – relapse in less than 6 months; R2 – relapse in more than 6 months. Results. We established an increase of the glutathione-transferase activity and a decrease of the GSH level in plasma after chemotherapy in R1 patients, and an opposite dynamic of glutathione-transferase and GSH in the R2 group. Thioredoxin level in plasma of all patients was lower than in the control group; differences in levels between groups were not statistically significant. GSTP1 105Val allele was more frequently present in patients than in the control group, and more frequently in R2 than in R1. Conclusion . The increase in plasma glutathione-transferase and glutathione-reductase levels can be a prognostic marker of early relapse. Thioredoxine dynamics do not correlate with the chemotherapy response. The presence of the GSTP1 105Val allele is a risk factor for ovarian cancer development, but a protective factor against early relapse.

ROLE OF GENETIC PREDISPOSITION, GENE POLYMORPHISM OF GLUTATHIONE-S-TRANSFERASE (GSTT1, GSTM1, GSTP1) AND SOME ADVERSE FACTORS IN DEVELOPMENT OF BRONCHIAL ASTHMA IN CHILDREN - RESIDENTS OF RADIOACTIVELY CONTAMINATED AREAS.

to determine the influence of hereditary predisposition, polymorphism of GSTT1, GSTM1, GSTP1 genes andenvironmental factors on the development of bronchial asthma in children - residents of radioactively contaminat-ed areas. School-age children-residents of radioactively contaminated areas with bronchial asthma,and those without clinical signs of respiratory pathology were examined. Genetic, medical, biological and social riskfactors were determined based on the study of anamnestic data and medical records. Ventilation lung capacity wasassessed by the method of computer spirometry. Molecular genetic studies were carried out using polymerase chainreaction (PCR) and restriction fragment length polymorphism (RFLP) for further analysis. Molecular genetic studies of the distribution of genotypes and frequencies of polymorphic variants of thegenes GSTT1, GSTM1, GSTP1 were performed in children living under long-term intake of 137Cs by food chains. It wasfound that in children with BA the tendency to frequency of the deletion variant of the GSTT1 and GSTM1 genes incomparison with children without bronchial and pulmonary pathology was increased. The study of distributing theGSTP1 A313G gene polymorphic variants revealed in children with BA a significant increase in the frequency of AG-genotype, compared with the data of reference group. Adverse factors that increase the risk of developing bron-choobstructive disorders and the probability of their implementation in the form of bronchial asthma in children -residents of RCA have been identified. It is established that among them the leading role is played by hereditarypredisposition to this disease. On the part of the child, such negative factors were unfavorable conditions of fetaldevelopment, the presence of signs of exudative-catarrhal diathesis, manifestations of allergies and frequent respi-ratory diseases from the first months of life. It was found that the risk of developing BA was significantly increasedin children with the GSTT1 and GSTM1 gene deletion genotypes; an increased risk of developing BA in children witha combination of the GSTP1 A313G gene polymorphism with deletion polymorphism of the GSTT1 or GSTM1 gene wasdetermined. Сonclusion. Оne of the leading mechanisms, due to which there is a realization of hereditary predisposition tobronchial asthma in children living under constant intake of radionuclides with a long half-life, is the polymorphismof certain glutathione-S-transferase genes, namely, GSTT1, GSTM1 and A313G gene deletion polymorphism and GSTP1gene polymorphism.

Influence of GSTP1 Polymorphism on the Clinical Outcomes of Patients With Advanced NSCLC Receiving First-Line Bevacizumab-Based Regimen: A Real-World Retrospective Study.

Background:This study was to investigate the influence of GSTP1 gene polymorphism on the clinical outcomes of patients with advanced non-small-cell lung cancer (NSCLC) receiving first-line bevacizumab plus chemotherapy regimen.Methods:A total of 128 patients with advanced NSCLC who were administered with bevacizumab-based first-line regimens were recruited in this study. Available blood specimen and peripheral blood mononuclear cells (PBMCs) of the patients were obtained for the analysis of polymorphism and GSTP1 gene mRNA expression, respectively. The association between genotype status and clinical outcomes and other variates was analyzed and presented.Results:The prevalence of rs1695 were in accordance with Hardy-Weinberg Equilibrium (P = .978). Patients with GG and AG genotypes were merged in a pattern of dominant inheritance to seek for the potentially clinical significance. Analysis of efficacy exhibited that the objective response rate (ORR) of patients with AA genotype and AG/GG genotypes were 62.1% (54/87) and 51.2% (21/41) (P = 0.245). Prognosis demonstrated that the median progression-free survival (PFS) of patients with AA genotype and AG/GG genotypes were 9.5 and 5.6 months, respectively (P = .007). Furthermore, the median overall survival (OS) of the two genotypes were 22.0 and 16.6 months, respectively (P = .003). In addition, adjusted in multivariate Cox analysis for OS, AG/GG genotype was an independent factor for OS. Interestingly, mRNA analysis suggested that the mRNA expression of GSTP1 in PBMC of the patients with AG/GG genotypes of rs1695 polymorphism was significantly higher than those of patients with AA genotype (P < .001).Conclusion:GSTP1 polymorphism rs1695 could be used for the prognostic evaluation of patients with advanced NSCLC receiving bevacizumab combined chemotherapy regimen.

Differences in Levels of Prostate Specific Antigen and Insulin-like Growth Factor 1 in GSTP1 Gene Polymorphism among Workers

Cadmium (Cd) is classified as a carcinogen in humans (IA). In addition to causing lung cancer, the incidence of prostate cancer due to Cd exposure based on epidemiological research has also increased. This study aims to identify the GSTP1 genotypic frequency distribution and its correlation with PSA and IGF-1 levels in Cd exposed and unexposed workers. The research design used was cross sectional in 23 exposed groups (weld workers) and 40 unexposed groups (office employees) with a total of 63 people. The measurement of PSA and IGF-1 levels was carried out using the ELISA method and identification of the GSTP1 gene polymorphism using the PCR-RFLP method. Data analysis using Mann-Whitney and Spearman correlation test. The results showed that there was a relationship between PSA levels and IGF1 (p &lt;0.01, r = 0.515) in all subjects. The results of identification of GSTP1 gene polymorphism were obtained as ile/ile genotypes as much as 30.2% and ile/val as much as 69.8%. There were no differences in PSA and IGF1 levels between ile/ile and ile/val genotypes (p&gt; 0.05). There was a relationship between PSA and IGF1 (p &lt;0.01, r = 0.569) in the group of Cd exposed workers and no differences in PSA and IGF1 levels between the ile/ile and ile/val genotypes (p&gt; 0.05). There was a relationship between PSA and IGF1 (p &lt;0.05, r = 0.342) in the unexposed group of workers and no differences in PSA and IGF1 levels between ile/ile and ile/val genotype (p&gt; 0.05).

CORRELATION ANALYSIS OF GSTP1 GENE POLYMORPHISM WITH MORBIDITY OF PRIMARY METASTATIC COLORECTAL CANCER

Colorectal cancer (CRC) is one of the most common malignancies. Susceptibility to malignant processes is mediated by genetically driven differences in the effectiveness of detoxification of potential carcinogens. One of the factors that may influence the risk of CRC is the glutathione-S-transferase (GST) gene family that encodes glutathione transferase enzymes. The GSTP1 gene is expressed both in normal and pathological conditions. Determining its specific alleles may be a marker of CRC. The aim of the research – to study GSTP1 gene polymorphism, which is likely to be more common among patients with primary metastatic colorectal cancer compared with healthy population. Materials and methods. The study involved 12 patients with primary metastatic colorectal cancer aged 43 to 72 years, the control group was represented by a sample of 31 people without cancer. Results. The incidence of advanced CRC in the presence of GSPT1 Val / Val (aa) polymorphism is statistically significantly higher than in the presence of Ile / Ile (AA) and Ile / Val (Aa) GSPT1 polymorphism. Conclusions. Among people with GSTP1 Val / Val (aa) polymorphism, primary CRC is 4.4 times more likely than among people with GSPT1 Ile / Ile (AA) and Ile / Val (Aa) polymorphisms, which are statistically significant (P &lt; 0.05). The obtained results indicate the possibility of conducting a genetic study of GSTP1 polymorphism to form groups of potential risk of CRC.

Genetic Polymorphism of GSTP1, GSTM1 and GSTT1 Genes and Susceptibility to Chronic Myeloid Leukaemia.

Background:The development of cancer results from an imbalance between exposure to carcinogens and the capacity of various enzyme systems engaged in activation or in the detoxification of xenobiotics. The aim of the present study is to investigate the association of GSTP1, GSTM1 and GSTT1 gene polymorphisms in susceptibility to Chronic Myeloid Leukaemia (CML). Methods:A total of 200 CML patients and 100 controls were enrolled in a case-control study with GSTM1 and GSTT1 analysis with PCR and GSTP1 analysis with PCR-RFLP. Results:The GSTT1 null genotype was significantly higher among CML patients suggesting that this genotype is associated with an increased risk of CML. It was found in 42% of cases as compared with 21% of the controls, (OR =2.78, 95% CI: 1.59 - 4.85; p-value =0.000). The presence of the GSTT1 genotype may thus be considered a protective factor for CML. The frequency of individuals carrying GSTM1 null genotype was slightly higher in the control group but this difference was not statistically significant. The GSTM1 null genotype was present in 35% of control cases and 34% of the CML patients, (OR=0.975, 95%CI: 0.58-1.58;p-value=0.863). Individuals with a combined GSTM1 null/GSTT1null genotype had an estimated 2.85-fold increased risk of CML, but no associated risk between GSTP1 Ile 105 Val polymorphism and CML was found (OR=1.99, 95% CI: 0.40 - 9.32; p-value = 0.417). Conclusions:No association between GSTP1 and GSTM1 with susceptibility to CML was found. GSTT1 genotype may be a protective factor for CML, while the null genotype shows association with developing CML.