GSTT1 Research Articles

A study of association between presence or absence of GSTT1 and GSTM1 and/or single nucleotide polymorphism in FABP2 and GSTP1 with incidence of diabetes type 2: A case-control study.

To assess the association of single nucleotide polymorphisms in fatty acid binding protein-2 (rs1799883) and glutathione S-transferase pi (rs1695) genes with presence/absence of glutathione S-transferase mu and glutathione S-transferase theta genes in type 2 diabetes. The cross-sectional case-control study was conducted at Institute of Molecular Biology and Biotechnology during March till September 2019 and comprised type 2 diabetes patients and non-diabetic controls from two districts in southern Punjab. Polymerase chain reaction, polymerase chain reaction-restriction fragment length polymorphism and tetra-primer amplification refractory mutation system-polymerase chain reaction were applied to investigate glutathione S-transferase theta, mu and pi genes as well as fatty acid binding protein-2, as appropriate. The association of single nucleotide polymorphisms in all genes with the disease were studied either individually or in various combinations. Data was analysed using Minitab 18. Of the 448 subjects, 248(55.4%) were patients and 200(44.6%) were controls. Overall there were 213(47.5%) males and 235(52.5) were females, and 141(31.5%) were aged 30-46 years. The presence of rs1799883 in fatty acid binding protein-2 (p=0.03) and the absence of glutathione S-transferase mu gene (p<0.001) had significant association with type 2 diabetes, while the presence of glutathione S-transferase theta and rs1695 in glutathione S-transferase pi genes were not associated with the disease. Individuals with glutathione S-transferase mu gene null and Ileu/Ileu or Ileu/Val genotype of rs1695 in glutathione S-transferase pi gene have potential to develop type 2 diabetes in their lifetime (p<0.05). The presence of rs1799883 in fatty acid binding protein-2 and the absence of glutathione S-transferase mu gene were found to play significantly in the development of type 2 diabetes.

Many hands make light work: CNV of GSTM1 effect on the oral carcinoma risk

BackgroundGenetic alterations of oral squamous cell carcinoma (OSCC) allow the understanding of the oral carcinogenesis and the identification of molecular biomarkers that aid the early diagnosis of the disease. The copy number variation (CNV) of GSTM1 and GSTT1 are promising targets because these two genes codify enzymes that perform the inactivation of tobacco carcinogens, which are the main risk factor of OSCC. However, the different levels of - detoxification mechanism in relation to each copy of the genes are unknown. Therefore, this study aimed to investigate the possible association of the CNV of GSTM1 and GSTT1 with the risk of development of OSCC. MethodsA total of 234 OSCC patients and 422 patients without any cancer diagnoses were recruited from Heliópolis Hospital from 2000 to 2011. The CNV was determined by TaqMan real-time PCR and the CopyCaller software. Odds ratio (OR) and 95% confidence interval (95% CI) values were calculated by Multiple Logistic Regression. ResultsMost OSCC patients reported they continued smoking high amounts of cigarettes despite the tumor diagnosis. The CNV of GSTM1 varied from zero to two copies and the analysis revealed that two copies of GSTM1 decreased by 53% the OSCC risk (OR 0.47; 95% CI 0.24–0.92) and the risk of the tumor was modified according to the interaction of the CNV of GSTM1 and the cigarette smoking consumption, which for the amount of 40 packs-year of cigarettes the OSCC risk diminished progressively according to the increase of copies of GSTM1. Although the GSTT1 gene varied from zero to three copies, none of them were associated with the tumor risk. ConclusionThe findings suggest that the CNV of GSTM1 might be applied as a tool for the surveillance of patients and the early detection of OSCC.

The Fagerström and AUDIT Tests as Probable Screening Tools in Oral Cancer and Their Correlation with CYP1A1, GSTM1, GSTP1, and GSTT1 Gene Expression.

Background: Cancer is currently a major public health problem worldwide, with a marked increase of about 70% in the number of expected diagnosed cases over the next two decades. The amount of tobacco and alcohol consumed is calculated based on the subjective information provided by the user. Tobacco exposure can be assessed using the Fagerström Test for Cigarette Dependence (FTCD) and alcohol consumption by the Alcohol Use Disorder Identification Test (AUDIT). Materials and Methods: Forty-eight subjects answered the Fagerström, and AUDIT tests and we studied them as likely screening tools for oral cancer and their correlation with the expression of CYP1A1, GSTM1, GSTP1, and GSTT1 genes by the RT-qPCR method. Results: There were significant differences in the AUDIT score and CYP1A1 expression between cancer and control groups. Participants in advanced stages, whether due to tumor size or regional metastasis, showed significant differences in the duration of tobacco use, FTCD, AUDIT score, and CYP1A1 expression when compared to patients in early stages. Among subjects without cancer, we found a significant correlation between participant age and GSTP1 expression. Furthermore, the expression of GSTP1 was significantly correlated with the number of cigarettes smoked per day, duration of tobacco use, and FTCD. Conclusions: Questionnaires designed to evaluate the degree of tobacco and alcohol exposure and dependence combined with gene expression tests can be useful to assess the risk of developing oral cancer. Furthermore, raising the awareness of individuals regarding their degree of dependence and encouraging them to participate in cessation programs are important educational measures for the prevention of tobacco-related malignancies.

Investigation of the Relationship between Genetic Polymorphisms in GSTM1 and GSTT1 Genes and Susceptibility to Lung Functional Abnormalities in Workers Exposed to Air Pollutants at Isfahan Steel Plant

Introduction: Gaseous air pollutants can cause oxidative stress, which can lead to lung damage by inducing inflammation. Polymorphisms in the glutathione S-transferase (GST) gene are involved in the pathogenesis of many diseases, including lung disease. Two glutathione S-transferase Mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) genes belong to this family, in which deletions occur and the resulting alleles are unable to produce active enzymes.&#x0D; Materials and Methods: In this study, 41 steel plant workers with impaired lung function were selected. Multiplex PCR technique was used to identify the genotyping of GST M1 and T1.&#x0D; Results: The results of the frequency of gene deletion among 41 patients showed that there were 10 individuals (17.2%) with deletion of GSTM1 gene, 4 individuals (11.8%) with deletion of GSTT1 gene. The results of the frequency of gene deletion among 50 healthy individuals (control group) also showed that there were 8 individuals (8.5%) with deletion of GSTM1 gene, and 12 individuals (8.3%) with deletion of GSTT1 gene. There were 7 individuals (14%) without deletion of GSTM1 and GSTT1 removal. The results of Chi-square test between healthy and sick groups showed no significance at the level of p &lt; 0.05.&#x0D; Conclusion: According to the results, it can be concluded that the sensitivity to lung function abnormalities in steel workers is directly related to the duration of employment.

Association between GSTM1, GSTT1 gene polymorphisms and asthma in adult patients from Tikrit population of Iraq

Introduction and Aim: Asthma is known as a polygenic and multifactorial disease. The underlying debate about the role of genetics in the development of asthma is still unclear. The objectives of this research are to examine whether the GSTM1 and GSTT1 gene polymorphisms are associated with asthma susceptibility. Materials and Methods: A total of 70 patients with asthma and 20 healthy individuals were investigated in this study. Genotyping was carried out by using PCR protocol for analysis of GSTM1 and GSTT1 null/positive genotypes. Results: Patients with asthma (34.285%) demonstrated a greater prevalence of the GSTM1, GSTT1 (-) genotype than the healthy subject (10%, P-value 0.012). A positive correlation was found between GSTT1, GSTM1 (+) genotype and healthy individuals (40%) compared with asthmatic patients (24.285%). Conclusion: The results of this research support the idea that GSTM1, GSTT1 (-) genotype may play critical roles in asthmatic inflammatory response. Further experimental investigations are needed to estimate the role of GSTM1 and GSTT1 polymorphisms in asthma.

Increased Risk of Acute Lymphoblastic Leukemia in Adult Patients with GSTM1 Null Genetic Polymorphism.

PurposeGlutathione S-transferases (GSTT1 and GSTM1) detoxify various endogenous and exogenous compounds and provide cytoprotective role against reactive species. This study aimed to assess the frequency of GSTT1, and GSTM1 polymorphisms in newly diagnosed Sudanese adult patients with acute lymphoblastic leukemia (ALL) and to evaluate the association of these polymorphisms with age, gender and type of ALL.Patients and MethodsThis case–control study included 128 adult Sudanese, untreated newly diagnosed patients with ALL, aged 18 to 74 years and 128 age-gender matched healthy controls. Deletional polymorphisms of GSTT1 and GSTM1 genes were genotyped through a multiplex polymerase chain reaction (PCR) assay using β-globin gene as an internal positive control.ResultsThe genotypic frequency of GSTT1 null polymorphism was 22.7% in cases and 14.8% in controls (OR = 1.68, P = 0.111). Statistically significant differences were noted in the frequencies of GSTM1 null polymorphism in cases and controls (OR = 3.7, P = <0.001). Combined GSTT1 null and GSTM1 null gene polymorphisms showed statistically significant difference in patients with ALL as compared to controls (OR = 6.5, CI 95% = 1.42–29.74, P < 0.001).ConclusionIrrespective of age at diagnosis, gender, and phenotype of ALL, GSTM1 null polymorphism either alone or in combination with GSTT1 null polymorphism poses significantly increased risk of developing ALL in adults.

18S rRNA gene sequencing for environmental aflatoxigenic fungi and risk of hepatic carcinoma among exposed workers

Aspergillus exposure causes an increase in aflatoxin (AF) levels among exposed workers thereby increasing their risk of developing hepatocellular carcinoma (HCC). This study attempted to determine the presence of airborne aflatoxigenic fungi in environment of waste water treatment plant (WWTP); and study the hepatic cancer risks among exposed workers, emphasizing the role of glutathione S-transferases (GST) gene polymorphism protecting against the risk of hepatic cancer development due to exposure to AFs. The study isolated and identified different Aspergillus species producing AFs in air samples from WWTP sites using 18S ribosomal ribonucleic acid (18S rRNA) gene sequencing technique. GST gene polymorphisms were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). A significant increase in blood AF levels was found among WWTP exposed workers. The occurrence of GSTT1& M1 gene polymorphism in 6% of the workers was accompanied by significant decrease in the levels of AFs and alpha fetoprotein (AFP). In conclusion, Aspergillus-producing AFs were found in air of WWTP. Continuous exposure to AF-producing fungi caused elevated AF-levels in exposed workers. However only workers with heterozygous GSTT1& M1 genotypes can detoxify AFs, thereby decreasing the risk of HCC development among exposed workers.

Proteome-wide identification of non-histone lysine methylation in tomato during fruit ripening

IntroductionHistone and non-histone methylations are important post-translational modifications in plants. Histone methylation plays a crucial role in regulating chromatin structure and gene expression. However, the involvement of non-histone methylation in plant biological processes remains largely unknown. MethodsThe methylated substrates and methylation sites during tomato fruit ripening were identified by LC-MS/MS. Bioinformatics of lysine methylated proteins was conducted to analyze the possible role of methylated proteins. The effects of methylation modification on protein functions were preliminarily investigated by site-directed mutation simulation. ResultsA total of 241 lysine methylation (mono-, di- and trimethylation) sites in 176 proteins were identified with two conserved methylation motifs: xxxxxxExxx_K_xxxExxxxxx and xxxxxxExxx_K_xxxxxxxxxx. These methylated proteins were mainly related to fruit ripening and senescence, oxidation reduction process, signal transduction, stimulus and stress responses, and energy metabolism. Three representative proteins, thioredoxin (Trx), glutathione S-transferase T1 (GST T1), and NADH dehydrogenase (NOX), were selected to investigate the effect of methylation modifications on protein activity. Mimicking demethylation led to decreased Trx activity but increased GST T1 and NOX activities. In addition, RT-qPCR exhibited that the expression of many genes that encode proteins subjected to methylation was upregulated during fruit ripening. ConclusionOur study suggests that tomato fruit ripening undergo non-histone lysine methylation, which may participate in the regulation of fruit ripening. It is the first report of methyl proteome profiling of non-histone lysine in horticultural crops.

Association of GSTM1 and GSTT1 Null Genotypes with Toluene Diisocyanate-Induced Asthma.

Background Toluene diisocyanate (TDI) causes occupational asthma by generating oxidative stress, leading to tissue injury and inflammation. Glutathione transferases (GSTs) are detoxifying enzymes that eliminate oxidative stress. We examined whether the genotypes of the GSTM1 and GSTT1 genes are associated with TDI-induced occupational asthma (TDI-OA). Methods The study population consisted of 26 asthmatics with a positive response to the TDI challenge (TDI-PA) and 27 asthmatics with negative responses (TDI-NA). GSTM1 and GSTT1 null and wild-type genotypes were determined using multiplex PCR. The plasma GSTM1 and GSTT1 protein concentrations were determined using ELISA. Results The GSTM1 null genotype was more frequent in the TDI-PA than in the TDI-NA (77.8 vs. 50.0%, OR = 3.5, p=0.03), while the frequency of the GSTT1 null genotype tended to be higher in the TDI-PA than in the TDI-NA (59.3 vs. 42.3%, OR = 1.98, p=0.21). When analyzed together, the GSTM1/GSTT1 null genotype was more frequent in the TDI-PA than in the TDI-NA (48.2 vs. 15.3%, OR = 6.5, p=0.04). The decline in the FEV in 1 s after TDI challenge was higher with the GSTM1/GSTT1 null than the GSTM1 wild-type/GSTT1 null genotypes (24.29% vs. 7.47%, p=0.02). The plasma GSTM1 level was lower with the GSTM1 null than with the GSTM1 wild-type genotypes both before (13.7 vs. 16.6 ng/mg, p=0.04) and after (12.9 vs. 17.1 ng/mg, p=0.007) the TDI challenge, while the GSTT1 level was not changed with either the GSTT1 null or wild-type genotype. Conclusions The GSTM1 null genotype, but not GSTT1 alone, may confer susceptibility to TDI-OA. However, the genetic effect of the GSTM1 null genotype may be enhanced synergistically by the GSTT1 null genotype. The genetic effect of GSTM1 was validated in the plasma as the GSTM1 protein level. Therefore, the GSTM1 and GSTT1 genotypes may be useful diagnostic markers for TDI-OA.

Association of GSTM1 and GSTT1 genes insertion/deletion polymorphism with colorectal cancer risk: A case-control study of Khyber Pakhtunkhwa population, Pakistan.

To evaluate the genetic association of glutathione S transferase M1 and glutathione S transferase T1 genes insertion/deletion polymorphism with the risk of colorectal cancer. This case-control study was conducted March 2018 and November 2019 at the University of Peshawar, Peshawar, Pakistan, and comprised blood samples from colorectal cancer patients and age- and gender-matched controls. Deoxyribonucleic acid was extracted from blood samples, and glutathione S transferase M1 and glutathione S transferase T1 genotyping was performed using polymerase chain reaction at the Institute of Radiation and Nuclear Medicine, Peshawar. Data regarding age, gender, location, smoking status, cancer stage and node involvement was collected on a predesigned proforma. Data was analysed using Minitab 17. The frequency of glutathione S transferase M1 was was significantly associated with colorectal cancer risk (p<0.01), while glutathione S transferase T1 null genotype showed non-significant association (p<0.43). The association between the combined deletion of glutathione S transferase M1 and glutathione S transferase T1 polymorphism and the colorectal risk was significant (p=0.011). Glutathione S transferase M1 and glutathione S transferase T1 deletions had non-significant association with age, smoking status, dwelling and tumour location (p>0.05) when compared with the wild genotypes in colorectal cancer cases. Glutathione S transferase M1 gene deletion was found to be associated with the risk of colorectal cancer development.

Genetic profiles of different ethnicities living in Karachi as regards to tobacco-metabolising enzyme systems and the risk of oral cancer.

To detect polymorphisms of CYP1A1, GSTM1 and GSTT1 gene loci among various tobacco-consuming ethnicities in an urban centre, and to relate these with susceptibility to oral cancer. The cross-sectional, case-control study was conducted at Ziauddin University, Karachi, and the Dow University of Health Sciences, Karachi, from 2011 to 2016, and comprised patients having oral squamous cell carcinoma in group A, with oral precancerous lesions in group B, and tobacco habit-matched controls in group C. Routine histopathology was followed by molecular analysis through polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism techniques. Data was analysed using SPSS 20. Of the 358 subjects, 150(42%) were in group A, 100(28%) in group B, and 108(30%) in group C. There were 190(53.1%) Urdu-speaking subjects, 42(11.7%) Memoni-speaking, 37(10.3%) Sindhi-speaking, 34(9.5%) Balochi-speaking, 25(7%) Pashto-speaking, 15(4.2%) Punjabi-speaking, and 15(4.2) of other ethnicities. Among the Urdu-speaking ethnicity, CYP1A1 MspI heterozygous variant was the most prevalent genotype ingroup A 50(66.7%), group B 37(62.7%) and group C 36(64.3%). The homozygous variant was equally distributed in group A 8(13.5%) and group B 10(13.3%), while it remained quite low in group C 4(7.1%). Homozygous genotype was most common in Pashto-speaking subjects in group A 4(57.1%). In Urdu-speaking subjects, GSTM1-null genotype was mostly found in group B 19(32.2%), while GSTT1-null genotype was most common in group A 12(16%). Other than Urdu-speaking, GSTM1-null variant was most frequent in Sindhi-speaking subjects in group B 8(80%). Intra-ethnic distribution of tobacco-metabolising enzyme genes can be considered an important contributor to oral cancer risk in the population of Karachi.

Gene-environment interactions related to maternal exposure to environmental and lifestyle-related chemicals during pregnancy and the resulting adverse fetal growth: a review.

BackgroundThere are only limited numbers of reviews on the association of maternal-child genetic polymorphisms and environmental and lifestyle-related chemical exposure during pregnancy with adverse fetal growth. Thus, this article aims to review: (1) the effect of associations between the above highlighted factors on adverse fetal growth and (2) recent birth cohort studies regarding environmental health risks.MethodsBased on a search of the PubMed database through August 2021, 68 epidemiological studies on gene-environment interactions, focusing on the association between environmental and lifestyle-related chemical exposure and adverse fetal growth was identified. Moreover, we also reviewed recent worldwide birth cohort studies regarding environmental health risks.ResultsThirty studies examined gene-smoking associations with adverse fetal growth. Sixteen maternal genes significantly modified the association between maternal smoking and adverse fetal growth. Two genes significantly related with this association were detected in infants. Moreover, the maternal genes that significantly interacted with maternal smoking during pregnancy were cytochrome P450 1A1 (CYP1A1), X-ray repair cross-complementing protein 3 (XRCC3), interleukin 6 (IL6), interleukin 1 beta (IL1B), human leukocyte antigen (HLA) DQ alpha 1 (HLA-DQA1), HLA DQ beta 1 (HLA-DQB1), and nicotinic acetylcholine receptor. Fetal genes that had significant interactions with maternal smoking during pregnancy were glutathione S-transferase theta 1 (GSTT1) and fat mass and obesity-associated protein (FTO). Thirty-eight studies examined the association between chemical exposures and adverse fetal growth. In 62 of the 68 epidemiological studies (91.2%), a significant association was found with adverse fetal growth. Across the studies, there was a wide variation in the analytical methods used, especially with respect to the genetic polymorphisms of interest, environmental and lifestyle-related chemicals examined, and the study design used to estimate the gene-environment interactions. It was also found that a consistently increasing number of European and worldwide large-scale birth cohort studies on environmental health risks have been conducted since approximately 1996.ConclusionThere is some evidence to suggest the importance of gene-environment interactions on adverse fetal growth. The current knowledge on gene-environment interactions will help guide future studies on the combined effects of maternal-child genetic polymorphisms and exposure to environmental and lifestyle-related chemicals during pregnancy.Supplementary informationThe online version contains supplementary material available at https://doi.org/10.1265/ehpm.21-00033.

Modification of the Genetic Polymorphism of Glutathione-S-Transferase (GSTM1 and GSTT1) in Motorcycle Drivers Exposed to BTEX in Cotonou

The glutathione-S-transferase genes mainly the GSTM1 and GSTT1 alleles are responsible for the synthesis of detoxication enzymes that can remove toxic substances. The objective of this study is to seek changes in the genetic polymorphism of glutathione-S-transferase GSTM1 and GSTT1 in motorcycle drivers exposed to BTEX. Our study group consists of 60 motorcycle drivers including 30 professional and 30 non-professional. Blood samples were preleveled from the study population in the EDTA tubes and DNA was extracted by the phenol/chloroform method. The PCR technique was used to determine the presence or absence of genes. Our results showed that the percentage of GSTM1 null genotype has a statistically significant difference (P = 0.02), while the percentage of GSTT1 null genotype was non-significant (P = 0.76) between the two groups. The percentage of deletion of both genes is higher in professional than non-professional motorcycle drivers. Air pollution in Cotonou by BTEX seems to influence the deletion of the GSTM1 and GSTT1 genes at a higher percentage among professional than non-professional motorcycle drivers.

Glutathione-S-transferase genetic polymorphism and risk of hepatotoxicity to antitubercular drugs in a North-African population: A case-control study.

GST non-functional genotypes can lead to the accumulation of toxic intermediates, resulting in liver damage and increasing susceptibility to ATDH. To investigate the impact of GST Mu (GSTM1), GST Theta (GSTT1) null genotypes, and GST Pi (GSTP1; adenosine (A)>guanine (G), rs1695) variant allele on the development of ATDH in Tunisian patients treated with anti-tuberculosis therapy. This was a case-control study including patients receiving anti-tuberculosis regimen. Cases (n=23) were tuberculosis patients presenting ATDH during two months of anti-tuberculosis drug therapy. Controls (n=30) were patients treated for tuberculosis, but presenting no ATDH. Genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism. No statistically significant association was observed between GSTM1 and GSTT1 homozygous null genotypes, and the risk of ATDH. A statistically significant association between GSTM1 and GSTT1 double null genotypes, and the risk of ATDH was found (p=0.033) between cases and controls. For GSTP1, the distribution of GG homozygous mutant genotype was significantly associated with ATDH compared with the wild and the transition A to G (AA+AG) genotypes. Double deletion of GSTM1 and GSTT1 may predispose to ATDH in a Tunisian population. Moreover, GSTP1 rs1695 (A>G) genotyping can predict susceptibility to developing ATDH.

Povezanost polimorfizama SOD2 i GST gena sa rizikom za nastanak i prognozom papilarnog karcinoma bubrežnog parenhima

Introduction: Redox imbalance is an important factor in both carcinogenesis and progression of renal cell carcinoma. Numerous studies are focused on finding potential biomarkers that can aid in early detection, as well as in monitoring disease progression. Among the candidates there are genes coding for antioxidant enzymes - superoxide dismutase 2 (SOD2) and glutathione S -transferase (GST). Aim: This study aims to assess the role of SOD2 and GST genes polymorphisms as risk biomarkers for papillary renal cell carcinoma (pRCC), along with their impact on the survival of these patients. Material and methods: This study included 39 patients and 336 controls. The following polymorphisms were determined by appropriate PCR methods: SOD2 (rs4880), GSTA1 C69T, GSTM1, GSTT1, and GSTP1 (rs1695) . ELISA method was used to measure 8-hydroxy-2'-deoxyguanosine (8-OHdG) and benzo(a)pyrene diol epoxide (BPDE)-DNA adducts plasma level. The effect of the polymorphisms on postoperative prognosis was examined using the available survival data. Results: There was no significant difference in the distribution of SOD2, GSTA1, GSTM1, and GSTT1 gene variants between patients and controls (p &gt; 0.05). However GSTP1 variant (GSTP1 * IleVal + ValVal) genotype was statistically significantly more frequent in patients compared to controls (p &lt; 0.05). Similarly, carriers of GSTP1 variant genotype were at significantly higher risk of developing carcinoma compared to carriers of GSTP1 reference genotype (OR = 16.103, 95% IP = 2.036 - 127.398). There was no association between the level of both 8-OHdG and BPDE-DNA adducts, and different genotypes (p &gt; 0.05). The investigated polymorphisms did not show any prognostic significance (p &gt; 0.05). Conclusion: These results indicate that the GSTP1 variant genotype was related to an increased risk of papillary renal cell carcinoma development. In order to fully understand the effect of investigated polymorphisms as a potential risk and prognostic biomarkers of this cancer, further research with a bigger sample size and longer follow-up are required.

Associations of Short-Term Exposure to Fine Particulate Matter with Neural Damage Biomarkers: A Panel Study of Healthy Retired Adults.

Exposure to fine particulate matter (PM2.5) is associated with various adverse health effects, such as respiratory and cardiovascular diseases. This study aimed to evaluate the association of PM2.5 with neural damage biomarkers. A total of 34 healthy retirees were recruited from Xinxiang Medical University from December 2018 to April 2019. Concentrations of PM2.5 constituents including 24 metals and nonmetallic elements and 6 ions, and 5 biomarkers of neural damage including brain-derived neurotrophic factor (BDNF), neurofilament light chain (NfL), neuron-specific enolase (NSE), protein gene product 9.5 (PGP9.5), and S100 calcium-binding protein B (S100B) in serum were measured. A linear mixed-effect model was employed to estimate the association of PM2.5 and its constituents with neural damage biomarkers. Modification effects of glutathione S-transferase theta 1 gene (GSTT1) polymorphism, sex, education, and physical activity on PM2.5 exposure with neural damage were explored. PM2.5 and its key constituents were significantly associated with neural damage biomarkers. A 10 μg/m3 increase in PM2.5 concentration was associated with 2.09% (95% CI, 39.3-76.5%), 100% (95% CI, 1.73-198%), and 122% (95% CI, 20.7-222%) increments in BDNF, NfL, and PGP9.5, respectively. Several constituents such as Cu, Zn, Ni, Mn, Sn, V, Rb, Pb, Al, Be, Cs, Co, Th, U, Cl-, and F- were significantly associated with NfL. The estimated association of PM2.5 with NSE in GSTT1-sufficient volunteers was significantly higher than that in GSTT1-null volunteers. Therefore, short-term PM2.5 exposure was associated with neural damage, and GSTT1 expression levels modified the PM2.5-induced adverse neural effects.

Role of Glutathione S-transferase Mu 1 and Glutathione S-transferases Theta 1 Polymorphism in the Risk of Developing Type 2 Diabetes Mellitus at Universitas Sumatera Utara Hospital, Medan

BACKGROUND: Diabetes mellitus is associated with an increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense. Glutathione S-transferases (GSTs) is group of multifunction antioxidant enzyme can be used as important biomarkers for DM.. GSTM1, T1 genes variant polymorphism result in decreased or loss of enzyme activity.&#x0D; AIM: The study aimed to evaluate the role of GSTM1 and GSTT1 gene polymorphism in the risk of developing T2DM.&#x0D; METHODS: GSTM1 and GSTT1 polymorphisms were genotyped in 87 T2DM patients and 87 healthy control group to analyze their association with T2DM susceptibility by using multiplex Polymerase Chain Reaction (PCR). PCR products were electrophoresed using agarose 2%. Odds ratio (OR) with 95% confidence interval (CI) and P value were calculated using SPSS software (version 21.0).&#x0D; RESULTS: The genotype distribution of GSTM1 and GSTT1 were not different between T2DM patients and healthy control group (p = 0.542, OR= 0.780, CI 95%=0.350-1.737 and p=0.879, OR=1.047, CI 95%=0.577-1.903). The genotype distribution of combination of GSTM1 and GSTT1 were also not not different between T2DM patients and healthy control group (p = 0.640, OR= 0.640, CI 95%=0.224-1.83 and p=0.551, OR=0.721, CI 95%=0.245-2.120.&#x0D; CONCLUSION: In summary, this study showed that GSTT1 null, GSTM1 null, the combination of GSTM1 null and GSTT1 null genotype or combination of GSTM1 null and GSTT1 positive (or contrary) did not have any risk of developing T2DM at Universitas Sumatera Utara Hospital, Medan.&#x0D;

Absence of Glutathione S-Transferase Theta 1 Gene Is Significantly Associated With Breast Cancer Susceptibility in Pakistani Population and Poor Overall Survival in Breast Cancer Patients: A Case-Control and Case Series Analysis

PurposeDeletion of Glutathione S-Transferase Theta 1 (GSTT1) encoding gene is implicated in breast cancer susceptibility, clinical outcomes, and survival. Contradictory results have been reported in different studies. The present investigation based on a representative Pakistani population evaluated the GSTT1-absent genotype in breast cancer risk and prognosis.MethodsA prospective study comprising case-control analysis and case series analysis components was designed. Peripheral blood samples were collected from enrolled participants. After DNA extraction, GSTT1 genotyping was carried out by a multiplex PCR with β-globin as an amplification control. Association evaluation of GSTT1 genotypes with breast cancer risk, specific tumor characteristics, and survival were the primary endpoints.ResultsA total of 264 participants were enrolled in the molecular investigation (3 institutions). The study included 121 primary breast cancer patients as cases and 143 age-matched female subjects, with no history of any cancer, as controls. A significant genetic association between GSTT1-absent genotype and breast cancer susceptibility (p-value: 0.03; OR: 2.13; 95% CI: 1.08-4.29) was reported. The case-series analysis showed lack of association of GSTT1 genotypes with menopause (p-value: 0.86), tumor stage (p-value: 0.12), grade (p-value: 0.32), and size (p-value: 0.07). The survival analysis revealed that GSTT1-absent genotype cases had a statistically significant shorter overall survival (OS) than those with the GSTT1-present genotype cases (mean OS: 23 months vs 33 months). The HR (95% CI) for OS in patients carrying GSTT1-absent genotype was 8.13 (2.91-22.96) when compared with the GSTT1-present genotype.ConclusionsThe present study is the first report of an independent significant genetic association between GSTT1-absent genotype and breast cancer susceptibility in a Pakistani population. It is also the foremost report of the association of this genotype with OS in breast cancer cases. Upon further validation, GSTT1 variation may serve as a marker for devising better population-specific strategies. The information may have translational implications in the screening and treatment of breast cancers.

Features of GSTM1, GSTT1 and GSTP1 Genetic Polymorphism in Nizhny Tagil Metallurgical Plant Workers with Cardiovascular Diseases

Background: The development of cardiovascular diseases is determined not only by working conditions but also by genetic characteristics of employees. Genetic GSTM1, GSTT1 and GSTP1 variations contribute to individual differences in responses to industrial chemicals and carcinogens. Objective: To study the features of the genetic polymorphism of the GSTM1, GSTT1, and GSTP1 genes in metallurgical plant workers with diseases of the cardiovascular system in the town of Nizhny Tagil, Sverdlovsk Region, Russian Federation. Materials and methods: The case cohort included 61 men aged 33 to 61 years (mean: 48.15 ± 7.50 years), working in the converter shop and suffering from heart diseases. The control cohort consisted of 29 conditionally healthy male employees, aged 23–56, of the same iron and steel works having no signs of a cardiovascular disease. The DNA was isolated from peripheral blood using a standard technique. Deletion polymorphism of GSTM1 and GSTT1 genes was determined by quantitative PCR; Ile105Val polymorphism of the GSTP1 gene was established by qPCR using a commercial test kit. Results: We observed no statistically significant differences between the cohorts for any of the studied genes. The frequency of occurrence of the combination of GSTM1 (0/0) and GSTT1 (0/0) in the cases and controls was 14 % and 11 %, respectively, but the difference was negligible. Conclusions: Our findings demonstrate that the presence of null genotypes of GSTM1, GSTT1, as well as the mutant GSTP1 allele and the associated loss of enzyme activity contribute little to the development of cardiovascular diseases in workers exposed to occupational hazards.

GST-Theta1 Enzyme Expression Levels in Brain Tumor and Their Relationship with the Clinical Data of the Patients

The most important drug metabolizing enzyme of the detoxification mechanism is known as Glutathione S-Transferase. GST enzymes may be associated with brain tumor epidemiology, clinical and demographic factors. The correlation between parameters such as changes in Glutathione S-transferase Theta1 proteins, tumor localizations, age, gender, alcohol use, smoking, chemotherapeutic/radiotherapeutic treatment status in normal and brain tumor tissues, diagnosed in neurosurgery department, were examined by immunohistochemistry. GST-Theta1 expressions were analyzed using immunostaining in samples from 149 patients diagnosed with brain tumors between 2016 and 2018. The mean age of the patient group was 49.44 years. 83 (58.45%) patients were male. After immunohistochemical staining, GST-T1 expression was found approximately 9,46 times higher in tumor tissues than in normal tissues (p&amp;lt;0.0001). Tumor tissues from patients who received chemotheraphy showed higher expression of GST-T1 than those who did not (p&amp;lt;0,05). In addition, GST-T1 expression level was observed at a significantly higher level in patients younger than 60 years of age compared to patients over 60 years (p&amp;lt;0.026; p&amp;lt;0.05). There was no statistically significant relationship between patients smoking behaviors, alcohol consumption, tumor localization and GST-T1 expressions. It is aimed to determine the GST-T1 protein expressions and to contribute to the examination of epidemiological and prognostic factors of brain tumors by comparing them with demographic and clinical data.