GSTT1 Polymorphisms Research Articles

Analysis of the influence of glutathione S-transferase (GSTM1 and GSTT1) genes on the risk of essential hypertension

Background Essential hypertension (EH) results from a complex interaction between environmental factors and an individual’s genetic background. Aim To assess the relationship between polymorphisms in GSTM1 and GSTT1 and the risk of EH. Subjects and methods A multiplex-PCR was used to identify the genotypic profiles of GSTM1 and GSTT1 in 160 patients and 210 controls. Results The frequency of GSTM1-null genotype was higher in patients younger than 61 years when compared to those over 61 years. Interestingly, GSTT1-null was significantly associated with the risk of EH (OR 4; 95% CI 2.6–6.3; p < 0.0001). While GSTM1-null showed no trend (OR 0.7; 95% CI 0.5–1.1, p = 0.12). Individuals carrying the combined GSTT1-null/GSTM1-null were 2.4 times more at risk for hypertension compared to those harbouring the combined GSTT1-present/GSTM1-present genotype (OR 2.4; 95% CI 1.3–4.4; p = 0.005). Additionally, the presence of the combined GSTT1-null/GSTM1-present was associated with an increased risk of EH compared to GSTT1-present/GSTM1-present carriers (OR 6.75; 95% CI 3.4–13.2; p < 0.0001). Conclusion This study showed that the GSTT1-null alone or in interaction with GSTM1-present or GSTM1-null was associated with a higher risk of hypertension. Moreover, the GSTM1-null seems to be associated with the age of onset of hypertension.

Evaluation of molecular markers GSTM1 and GSTT1 and clinical factors in breast cancer: case-control study and literature review

The study was conducted to evaluate the frequency of polymorphisms in GSTM1 and GSTT1 genes in patients with breast cancer compared with individuals without history of cancer, and the association of these polymorphisms with clinical/epidemiological parameters. There were evaluated 752 women (219 patients and 533 controls). Molecular analysis was performed by the Polymerase Chain Reaction (PCR). Statistical analysis was used multiple logistic regression and descriptive statistics. Age ≥ 50 years (OR = 3.22, 95% CI = 2.30–4.51, p < 0.001) and alcohol consumption (OR = 1.60, 95% CI = 1.13–2.27, p = 0.008) were associated to the development of breast cancer, while smoking and null genotypes GSTM1 and GSTT1 presented no association. GSTM1 and GSTT1 polymorphisms presented no relationship with the clinical and histopathological parameters or molecular subtypes of breast cancer. Ninety-two percent of tumours were invasive ductal, 66% were grade II, 65% were larger than 2 cm, the stages II (35.3%) and III (31.2%) were the most prevalent, and 47.7% were molecular subtype luminal B. Individuals aged ≥ 50 years and alcohol consumers have more chance to developing breast cancer. GSTM1 and GSTT1 polymorphisms are not associated to the risk of breast cancer.

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.

No association between GSTM1 and GSTT1 deletion polymorphisms and Amyotrophic Lateral Sclerosis: a genetic study in Brazilian patients

The glutathione S-transferases superfamily (GSTs) act on the detoxification process of xenobiotics and oxidative stress products. The relevance of gene-environment interactions in the development of Amyotrophic lateral sclerosis (ALS) encourages further investigation into the role of genetic factors, such as GSTM1 and GSTT1 deletion polymorphisms. This case-control study evaluated the association of GSTM1 and GSTT1 deletion polymorphism and ALS susceptibility. We genotyped 101 case-patients and 119 controls with multiplex real-time PCR (qPCR) and collected clinical and demographic data from medical records and questionnaires. Our findings demonstrated that alcohol intake was predominant in ALS patients and was significantly associated with the development of the disease (p = 0.01). However, we found no association between ALS risk and GSTM1 (p = 0.85) and GSTT1 (p = 0.90) polymorphisms, even when we combined both genotypes. We analyzed a sample of Brazilian patients, a population within which few studies exist about this rare disease. Thus, new insights seeking the relationship between ALS and mutations, polymorphisms, or the expression of other cell detoxification pathway genes should be encouraged and will provide additional information on the role of antioxidant mechanisms and oxidative stress in the pathogenesis of the disease.

Relationship between GSTM1 and GSTT1 polymorphisms and HPV infection: a systematic review.

Human Papillomavirus (HPV) is the most important risk factor for cervical cancer, although not the only one. The allelic polymorphism of enzymes acting on carcinogen metabolism has shown to influence the risk of both intraepithelial lesions and cervical carcinogenesis. Several studies found an association between GSTM1/GSTT1 null genotypes and risk of cancer. This research aimed to review studies addressing the relationship between GSTT1 and GSTM1 and HPV infection in women, with or without cervical pathologies. A database search was conducted in four databases - PubMed, LILACS, SciELO, and Virtual Health Library - using the following descriptors: Glutathione transferase, HPV, and Genetic polymorphism. In total, we found 319 studies. After screening titles and abstracts, 27 articles were selected for full-text read, among which 20 were excluded and 7 were included in the review. No study has exclusively approached the relationship between the virus and GSTM1/GSTT1 variants. However, studies investigating the association between single nucleotide polymorphisms (SNPs) and cervical lesions or cancer found a probable relationship between them and infections with high-risk oncogenic subtypes. Although inconclusive, GSTT1 null alleles were more common in women with more aggressive HPV than GSTM1.

Formaldehyde in Hospitals Induces Oxidative Stress: The Role of GSTT1 and GSTM1 Polymorphisms.

Despite the toxicity and health risk characteristics of formaldehyde (FA), it is currently used as a cytological fixative and the definition of safe exposure levels is still a matter of debate. Our aim was to investigate the alterations in both oxidative and inflammatory status in a hospital working population. The 68 workers recruited wore a personal air-FA passive sampler, provided a urine sample to measure 15-F2t-Isoprostane (15-F2t-IsoP) and malondialdehyde (MDA) and a blood specimen to measure tumour necrosis factor α (TNFα). Subjects were also genotyped for GSTT1 (Presence/Absence), GSTM1 (Presence/Absence), CYP1A1 exon 7 (A > G), and IL6 (−174, G > C). Workers were ex post split into formalin-employers (57.3 μg/m3) and non-employers (13.5 μg/m3). In the formalin-employers group we assessed significantly higher levels of 15-F2t-IsoP, MDA and TNFα (<0.001) in comparison to the non-employers group. The air-FA levels turned out to be positively correlated with 15-F2t-IsoP (p = 0.027) and MDA (p < 0.001). In the formalin-employers group the MDA level was significantly higher in GSTT1 Null (p = 0.038), GSTM1 Null (p = 0.031), and CYP1A1 exon 7 mutation carrier (p = 0.008) workers, compared to the wild type subjects. This study confirms the role of FA in biomolecular profiles alterations, highlighting how low occupational exposure can also result in measurable biological outcomes.

Glutathione S-Transferase Polymorphisms and Clinical Characteristics in Autism Spectrum Disorders.

Background: Autism spectrum disorders (ASD) are a heterogeneous group of developmental disorders, with different levels of symptoms, functioning, and comorbidities. Recent findings suggested that oxidative stress and genetic variability in glutathione S-transferases (GSTs) might increase the risk of ASD development. We aimed to determine whether GST polymorphisms influence the severity of symptoms as well as the cognitive and adaptive abilities in children with ASD.Methods: The sample included 113 ASD cases. All participants were genotyped for GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms. The clinical characteristics were determined with Autism Diagnostic Interview-Revised (ADI-R) in all of the participants. In non-verbal participants, we explored the adaptive functioning using the Vineland Adaptive Behavior Scale II, while in verbal participants, we used the Wechsler Abbreviated Scale of Intelligence (WASI).Results: It was shown that the GSTA1*CC genotype was a predictor of a lower non-verbal communication impairment as well as of a lower chance of having seizures during life. GSTM1-active genotype predicted a higher adaptive functioning. The predictive effect of GSTA1, GSTM1, and GSTT1 genotype was moderated by exposure during pregnancy (maternal smoking and medication). The GSTP1*IleIle genotype was significantly associated to a better cognitive functioning in children with ASD.Conclusion: Besides the complex gene-environment interaction for the specific risk of developing ASD, there is also a possible complexity of interactions between genetic and environmental factors influencing the level of symptoms and impairment in people with ASD. Detoxification and antioxidant enzymes, such as GSTA1, might contribute to the core of this complexity.

Polymorphisms in xenobiotic metabolism-related genes in patients with hepatocellular carcinoma: a case–control study

This study was performed to investigate the relationship between polymorphisms in microsomal epoxide hydrolase (mEH; Tyr113His and His139Arg substitution) and glutathione S-transferase (GST; GSTM1 deletion, GSTT1 deletion, and GSTP1.Ala114Val substitution) and their correlation with clinico-histopathological features in hepatocellular carcinoma (HCC). We evaluated environmental risk factors and genetic alterations in 556 individuals (86 cases and 470 controls). PCR multiplex for GSTM1 and GSTT1, polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) for GSTP1, and real-time PCR for mEH were performed. Statistical analyses were performed using multiple logistic regression tests. Age over 48 years (p < 0.001) and alcohol consumption (p = 0.021) were the predictors of increased risk of developing HCC. GSTP1.Ala114Val for all regression models (p < 0.05), except the recessive model, and the GSTT1 null genotype (odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.21–0.87, p = 0.019) were predictors of an increased risk of developing HCC. Polymorphic GSTT1, GSTM1, GSTP1.Ala114Val, and mEH.His139Arg and wild-type mEH.Tyr113His (OR = 5.04; 95% CI = 1.59–16.04; p = 0.006) were associated with HCC. Age over 48 years, alcohol consumption, and the presence of polymorphic variants of GSTP1 and GSTT1 were associated with the risk of developing HCC.

Genetic polymorphisms of metabolic enzyme genes associated with leukocyte mitochondrial DNA copy number in PAHs exposure workers.

BackgroundPolycyclic aromatic hydrocarbons (PAHs) exposure had been reported to be a risk factor of mtDNAcn in our early study. However, the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs‐Exposure workers has not been fully evaluated.AimThe aim of the study was to explore the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs‐Exposure.Methods and ResultsWe investigated the effects of metabolic enzymes' genetic polymorphisms on mtDNAcn among 544 coke oven workers and 238 office staffs. The mtDNAcn of peripheral blood leukocytes was measured using the Real‐time quantitative polymerase chain reaction (PCR) method. PCR and restriction fragment length was used to detect five polymorphisms in GSTT1, GSTM1, GSTP1 rs1695, CYP2E1 rs6413432, and CYP2E1 rs3813867. The mtDNAcn in peripheral blood leukocytes was significantly lower in the exposure group than that in the control group (p < .001). The 1‐OHPYR had an increasing trend with the genotypes AA→AG → GG of GSTP1 rs1695 in the control group. Generalized linear model indicated that the influencing factors of mtDNAcn were PAHs‐exposure [β (95% CI) = −0.420 (−0.469, −0.372), p < .001], male [β (95% CI) = −0.058 (−0.103, −0.012), p = .013], and AA genotype for GSTP1 rs1695 [β (95% CI) = −0.051 (−0.095, −0.008), p = .020].ConclusionThe individuals carrying the AA genotype of GSTP1 rs1695 may have a lower mtDNAcn due to their weaker detoxification of PAHs.

Role of Antioxidant Gene Polymorphisms in Risk and Prognosis of Chronic Myeloid Leukemia

Introduction: We aimed to investigate the possible role of antioxidant enzyme polymorphisms CAT -21A/T (rs7943316), CAT -262C/T (rs1001179), GPX1 -198C/T (rs1050450), MPO -463G/A (rs2333227), GSTM1 (rs366631) &amp; GSTT1 (rs17856199) with susceptibility to chronic myeloid leukemia (CML) and their association with tyrosine kinase inhibitor (TKI, imatinib) response.Methods: Six single nucleotide polymorphisms (SNPs) in antioxidant enzyme genes were genotyped in a total of 325 samples, of which 125 were from CML patients and 200 from healthy controls. The SNPs were correlated with various confounding variables lke BCR-ABL1 levels and tyrosine kinase domain mutation status in CML patients.Results: Genotyping results revealed statistically significant associations with CAT -21A/T (p=0.037) and GPX1 -198C/T (p=&lt;0.0001) polymorphisms with risk of CML. No associations were observed between CAT -262C/T, MPO -463G/A, GSTM1 &amp; GSTT1 polymorphisms and CML. The CAT -21A/T polymorphism conferred 2.95 folds increased risk of CML under co-dominant model (p=0.024) and 2.51 folds risk under dominant models (p=0.05). In addition, the haplotypes of CAT -21A/T and -262C/T polymorphisms, ATCC and ATCT conferred higher incidence of CML risk by 2.67 times (p=0.05) and 2.99 times (p=0.045). The GPX1 -198C/T polymorphism conferred significantly increased risk of CML under co-dominant model [CC vs CT (p=&lt;0.0001), CC vs TT (p=&lt;0.0001)] and dominant models [CC vs CT+TT (p=&lt;0.0001)]. The heterozygous GPX1 CT genotype frequency significantly elevated in poor molecular responders (p=0.005) and TKD mutation carriers (p=0.114) as compared to respective groups.Conclusions: Our results suggest that the reduced activity of antioxidant enzymes caused by the CAT -21A/T and GPX1-198C/T polymorphisms might contribute to increased risk of CML. In addition, the GPX1-198C/T polymorphism was associated with poor molecular response and acquired TKD mutations. Hence, the present study indicates that defective antioxidant defense system might have a strong influence on CML susceptibility and TKI (imatinib) response through oxidative stress.

The association of glutathione S-transferase T1 and M1 deletions with myocardial infarction

Glutathione S-transferases (GSTs) are the family of enzymes involved in the second line of defense against oxidative stress (OS). The lack of GSTT1/GSTM1 enzyme quantity or activity, due to the presence of homozygous deletion compromises antioxidative defense resulting in OS. OS is the critical mechanism in the pathophysiology of atherosclerosis, coronary artery disease, and myocardial infarction (MI). The increase in reactive oxygen species together with the process of apoptosis plays a role in left ventricular remodeling (LVR) after MI. The associations of GSTT1 and GSTM1 gene polymorphisms with the risk of MI are inconsistent. The aim was to analyze the association of GSTT1/GSTM1 null genotypes with first MI and LVR 8 months after the MI. The study involved 330 controls and 438 consecutive patients with symptoms and signs of first MI. The subgroup of 150 MI patients was prospectively followed up for 6 months. Evidence of maladaptive LVR was obtained by 2D Doppler echocardiography 3–5 days and 6 months after the MI. A multiplex polymerase chain reaction was used to detect the deletion in GSTT1 and GSTM1 genes. GSTM1 null genotype was significantly and independently associated with first MI (adjusted OR = 1.45 95% CI 1.03–2.03, p = 0.03). Association of double null genotypes with maladaptive LVR in patients 6 months after the first MI was no longer significant after adjustment for factors that differed significantly between patients with and without maladaptive LVR. This study demonstrated the association of GSTM1 null genotypes with the risk of MI in the Serbian population.

Polymorphism of GSTM1,GSTT1,GSTP1, and GSTA1 genes In Iraqi Population

One of the phase II enzymes that are responsible for detoxification of the body are Glutathione S-transferases (GSTs). Type and frequency of polymorphism of GSTs differ among the population. The current paper was designed to detect the polymorphisms in GSTM1, GSTT1, GSTP1 and GSTA1 genes among the Iraqi population, and the results were compared with other population. Data will be collected in the future to obtain a genetic map of the Iraqi population. To our knowledge, this study is the first done on the Iraqi population. In this study blood samples were collected from 110 healthy individuals (51 males and 59 females) aged between 15-50 years. The presence or absence of GSTM1 and GSTT1 genes was identified by multiplex-PCR. In addition, PCR-RFLP was used to detect polymorphism of GSTP1 (Ile105Val) and GSTA1 (A*/B*). The study revealed the frequencies of GSTM1 null, GSTT1 null, GSTP1 (Ile105Val), and GSTA1 A*/B* were 34.55%, 25.45%, 45.46%, and 41.82% respectively. The most frequently observed combinations were GSTM1 Present/GSTT1 Present/Ile/Val/A*/A* (18.18%). For the first time in Iraq by this study, four sequences were recorded in NCBI under the following accession numbers LC081235.1, LC090205.1, LC081236.1, and LC090206.1. These findings provide us the basic data for genotypes distribution and allele frequencies of GSTM1, GSTT1, GSTP1 and GSTA1 in the Iraqi population, and this is open a new prospect for further investigations by researchers in identifying differences between individuals in the genetic susceptibility of various diseases caused by environmental gene, rather than depending on results obtained from other populations.

Association of temperament with genetic polymorphisms in SOD1, GSTM1 and GSTT1 genes.

Due to its accessibility, efficacy, and affordability, traditional medicine (TM) is the main source of health services for many people in the world. Nevertheless, in spite of its benefits, there are still many issues about the principles of TM which demand further declaration. One of the essential principles of Iranian traditional medicine (ITM) is temperament (mizaj), which efficiently applied in diagnosis and therapy of illnesses. In this study we aimed to explore the association of GSTM1/T1, and SOD1 50 bp Ins/Del polymorphisms with combined groups of temperament. The study was conducted in 217 healthy males from Fars province, southern Iran. The self-reported mizaj questionnaire was applied to identify the participants’ temperament. Then individuals with temperate, warm/moist, and warm/dry temperament were entered in the study. To determine the genotype of GSTM1, GSTT1, and SOD1, the polymerase chain reaction (PCR)-based method was performed. As the results of χ2 analysis showed, the frequency of GSTT1, GSTM1, and SOD1 polymorphisms in temperate group was not significantly differ from that in each of warm/moist and warm/dry groups. Further research with larger samples are suggested to clarify the association between temperament and biomolecular features.

Influence of genetic polymorphisms in glutathione-S-transferases gene in response to imatinib among Brazilian patients with chronic myeloid leukemia

Polymorphism in metabolizing enzymes can influence drug response as well as the risk for adverse drug reactions. Nevertheless, there are still few studies analyzing the consequence of polymorphisms for the Glutathione-S-transferases (GST) gene to drug response in chronic myeloid leukemia (CML). This study reports, the influence of GSTP1*B and GSTT1/GSTM1null polymorphisms in response to imatinib in CML patients in a Brazilian population. One hundred thirty-nine CML patients from the Clinical Hospital of Goiânia, Goiás, Brazil, treated with imatinib were enrolled in this study. Genotyping of GSTT1 and GSTM1 genes deletions were performed by qPCR and of GSTP1 gene was performed by RFLP-PCR. The frequency of GSTP1*1B, GSTT1 and GSTM1null polymorphisms were determined for all patients. The influence of each patient's genotypes was analyzed with the patient's response to imatinib treatment. Brazilian CML patients revealed GSTT1 and GSTM1 genes deletions. GSTT1 deletion was found in 19.3% of patients and GSTM1 deletion in 48.7% of patients with CML. GSTT1/GSTM1 deletion was found in 11.7% in Brazilian CML patients. The "G allele" of GSTP1*B, is associated with later cytogenetic response in imatinib therapy. While, the gene presence combined with GG genotype (GSTM1 present/GSTPI-GG) conferred a tend to a later cytogenetic response to patients. GSTP1*B and GSTT1/GSTM1null polymorphisms influence treatment response in CML. Brazilian CML patients presenting GSTP1 AA/AG genotypes alone and in combination with GSTT1 null reach the cytogenetic response faster, while patients presenting GSTP1-GG and GSTMI positive genotypes may take longer to achieve cytogenetic response. As a result, it allows a better prognosis, with the use of an alternative therapy, other than reducing treatment cost.

GST T1, M1, and IRS-1 G972R Genetic Variants Association to Gestational Diabetes Mellitus (GDM) in Egyptian Women: Linkage to Maternal Hyperglycemia.

Gestational Diabetes Mellitus (GDM) shares in part the pathogenic mechanisms of multiple genetic interactions. Some of the T2D susceptibility genes are encountered in association with GDM. We aimed to investigate GST T1, M1, and G972R IRS-I gene polymorphisms with the risk of developing GDM. In this randomized case-control study, pregnant women with GDM were genotyped by PCR analysis for glutathione s-transferase-T1, M1 variant polymorphisms. RFLP was done for the G972R IRS 1 gene. Their newborns were additionally assayed for the whole of the clinical, laboratory, and genetic aspects. The T allele IRS-1rs1801278 TT genotype was more frequently detected in GDM mothers in comparison to healthy control ones [for TT homozygous variant; OR(CI 95%): 2.05(1.09-3.87, p: 0.025)]. Furthermore, GST T1 null was significantly presented in GDM mothers than those of control mothers [OR (CI95%: 0.29 (0.084-1.02), p:0.04]. Added to the significant correlation of glycemic indices to clinical parameters of infants born to GDM, the M1-null genotype of GST was significantly correlated (p<0.05) to abnormal values of respiratory rates and 1 minute-APGAR score noted for extra NICU care. Our results suggested that GST T1null and IRS-1 TT genotypic variants were claimed for GDM development among Egyptian women with a possible impact on their newly born infants.

The role of polymorphisms in glutathione-related genes in asbestos-related diseases.

BackgroundThe study investigated the influence of GCLC, GCLM, GSTM1, GSTT1 and GSTP1 polymorphisms, as well as the influence of interactions between polymorphism and interactions between polymorphisms and asbestos exposure, on the risk of developing pleural plaques, asbestosis and malignant mesothelioma (MM).Subjects and methodsThe cross sectional study included 940 asbestos-exposed subjects, among them 390 subjects with pleural plaques, 147 subjects with asbestosis, 225 subjects with MM and 178 subjects with no asbestos-related disease. GCLC rs17883901, GCLM rs41303970, GSTM1 null, GSTT1 null, GSTP1 rs1695 and GSTP1 rs1138272 genotypes were determined using PCR based methods. In statistical analysis, logistic regression was used.ResultsGSTT1 null genotype was associated with the decreased risk for pleural plaques (OR = 0.63; 95% CI = 0.40–0.98; p = 0.026) and asbestosis (OR = 0.51; 95% CI = 0.28–0.93; p = 0.028), but not for MM. A positive association was found between GSTP1 rs1695 AG + GG vs. AA genotypes for MM when compared to pleural plaques (OR = 1.39; 95% CI = 1.00–1.94; p = 0.049). The interactions between different polymorphisms showed no significant influence on the risk of investigated asbestos-related diseases. The interaction between GSTT1 null polymorphism and asbestos exposure decreased the MM risk (OR = 0.17; 95% CI = 0.03–0.85; p = 0.031).ConclusionsOur findings suggest that GSTT1 null genotype may be associated with a decreased risk for pleural plaques and asbestosis, may modify the association between asbestos exposure and MM and may consequently act protectively on MM risk. This study also revealed a protective effect of the interaction between GSTP1 rs1695 polymorphism and asbestos exposure on MM risk.

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.

Impact of xenobiotic-metabolizing gene polymorphisms on breast cancer risk in South Indian women.

Functional variants of the xenobiotic-metabolizing genes (XMG) might modulate breast cancer (BC) risk by altering the rate of metabolism and clearance of myriad types of potent carcinogens from the breast tissue. Despite mounting evidence on the role of XMG variants on BC risk, the current knowledge regarding their influence on BC development is still fragmentary. The present study examined the candidate genetic variants in CYP1A1, NQO1, GST-T1, GST-M1, and GST-P1 in 1002 subjects (502 BC patients and 500 disease-free women). PCR-RFLP was employed to genotype the mono-nucleotide variation in CYP1A1, NQO1, and GST-P1, and allele-specific PCR was used to detect the deletion polymorphism in GST-T1 and GST-M1 genes. Regarding CYP1A1-M1 polymorphism, the heterozygous TC and mutant CC genotype conferred 1.47-fold (95% CI 1.13-1.91, p = 0.004) and 1.84-fold (95% CI 1.17-2.91, p = 0.009) elevated risk of BC. GST-T1 null genotype was associated with increased BC risk (OR 1.47; 95% CI 1.02-2.11, p = 0.037). For the NQO1 C609T variant, the mutant T allele was associated with BC risk with an odds ratio of 1.22 (95% CI 1.02-1.48, p = 0.034). Combinatorial analysis indicated that the presence of NQO1*2 (CT), CYP1A1-M1 (CC), and GST-P1 rs1695 (AG) genotypes conferred 16.7-fold elevated risk of BC (95% CI 3.65-76.85; p < 0.001). Moreover, GST-M1 null genotype was associated with the development of larger primary breast tumors. Xenobiotic-metabolizing gene polymorphisms may play a crucial role in mammary carcinogenesis in South Indian women.

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.

Effects of GSTT1 and GSTM1 polymorphisms in glutathione levels and breast cancer development in Brazilian patients.

Polymorphisms in the glutathione transferase enzymes (GSTs) genes have been associated with susceptibility to develop breast cancer (BC), but few are known regarding its role on this disease prognosis and impact on antioxidant status. This study evaluated the polymorphisms of GSTM1 and GSTT1 genes and their relationship with BC susceptibility and prognostic, as well as its impact on plasma reduced glutathione (GSH) levels. The present study included 121 women with invasive ductal BC and 151 healthy controls. Polymorphisms analyses were performed using the polymerase chain reaction (PCR) technique and GSH levels were measured with the Ellman's reagent. GSTT1 (OR 1.29; p = 0.39) and GSTM1 (OR 1.03; p = 0.91) polymorphisms did not show any association with BC susceptibility. The mean concentration values in nmol/L of GSH were 20.37 ± 5.82 for patients with null genotypes for both genes, 19.75 ± 3.47 for null GSTT1, 17.22 ± 1.35 for active GSTT1, 18.82 ± 1.96 for absent GSTM1, and 16.59 ± 1.66 for active GSTM1, but no significance was found. Therefore, it can be concluded that the behavior of these polymorphisms concerning BC might be not only related to the absence of enzymatic expression but may also be related to the body's response with its antioxidant mechanisms and it should be further studied.