Polymorphism in GSTM1 and GSTT1 genes influence DNA damage in personnel occupationally exposed to volatile anaesthetics (VA), from Peshawar, Pakistan

ObjectivesThe objective of this study was to assess the influence of antioxidant gene GSTM1 and GSTT1 on DNA damage in personnel occupationally exposed to volatile anaesthetics (VA).MethodsThe study groups were composed of 50 exposed subjects (anaesthesia workers) and 49 controls. Blood samples were collected from both subjects. DNA damage was analysed through the comet assay technique. Biomarker genes GSTM1 and GSTT1 were inspected through PCR technique for polymorphism.ResultsThe comet assay technique showed that the Total Comet Score (TCS) in exposed subjects was significantly higher (p=0.0001) than the control. Age and smoking had significant effects on TCS in the study groups (p<0.05). Duration of occupational exposure had significant positive correlation (r=0.755, p<0.001) with DNA damage. The null polymorphism in GSTM1 and GSTT1 gene showed a significant effect (p<0.001 and p<0.000) on the DNA damage.ConclusionsThe polymorphism in GSTM1 and GSTT1 gene significantly damage DNA in personnel occupationally exposed to VA.

DEVELOPMENT OF PRIMARY OPEN-ANGLE GLAUCOMA AND DELETION POLYMORPHISM OF THE GLUTATHIONE-S-TRANSFERASE GENES

The aim of the research. To investigate the association of the development of primary open-angle glaucoma with deletion polymorphism of glutathione-S-transferase genes. Materials and methods. Under our observation there were 172 patients, residents of Ukraine with primary open-angle glaucoma I–IV stages. Analysis of the deletion polymorphism of GSTM1 and GSTT1 genes was performed by real-time polymerase chain reaction using unified TaqMan Mutation Detection Assays Life-Technology (USA) test systems. Statistical analysis of the obtained data was performed using the MedStat package and the statistical package MedCalc v.15.1 (MedCalc Software bvba). Results and discussion. The detection of null alleles of the GSTM1 gene was observed in 39 % of patients in the control group, in patients with POAG a significant increase in the frequency of deletion polymorphism to 50–56 % was observed with the progression of the disease in stages II-IV. In patients with stage IV disease, the effect of the zero GSTM1- null allele on POAG course was determined (χ2=3.97; p=0.047), and the null allele of GSTM1 doubled the probability of developing the disease (OR=2.01; 95 % CI=1.01–4.01) in patients of group 4 compared with control. The null allele of the GSTT1 gene in the control group was found in 31 %, an increase in the frequency of the GSTT1-null allele was also observed in the second and fourth stages of POAG from 41 % to 54 %. Statistically significant differences of GSTT1 gene allele frequencies were determined between the control group and all patients with POAG (χ2=4.43; p=0.03), between the control and the 4th group (χ2=7.64; p=0.01), and between the 1st and 4th groups (χ2=5.52; p=0.02). An association with the development of POAG (χ2=4.43; p=0.03) was determined for the deletion polymorphism of the GSTT1 gene when comparing the control group with the data of all patients with POAG (1–4 groups). At stratification by stages of POAG (that is, by groups of patients), an association with the development of POAG was determined only in patients of group 4 (χ2=7.64; p=0.01) compared with the control group. Conclusions. The association of the null allele of the GSTT1 gene with POAG was established (p=0.03). The presence of the GSTT1-null allele significantly increased the risk of developing POAG (OR=1.75; BI=1.04–2.96) compared with the control group. The presence of null alleles (GSTM1-null and GSTT1-null) of the GST deletion polymorphism significantly increased the risk of stage IV POAG (OR=2.01; BI=1.01–4.01 and OR=2.66; VI=1.32–5.37, respectively) compared with the control group, which indicated the effect of zero alleles on the rapid progression of the disease.

Detection of glutathione S-transferases M1, T1 gene deletions among cancer patients in Mongolia

Various types of toxic xenobiotic and electrophilic compounds, which were formed from the glutathione S-transferases cell metabolism and the oxidation stress, are the group enzymes with detoxification roles that are involved in the metabolism phase II. During the GSTM1 and GSTT1 gene homozygous deletion, the above enzymes completely lose their activity and consequently somatic mutation is formed. Furthermore, it is considered that it might have increased the risk of cancer. Therefore, the research works which connected the GSTMI and GSTTI gene deletion with the cancer of kidney, lung, prostate, breast, stomach, esophagus, large and narrow intestines. In this study, two gene deletion distribution is detected for cancer patients. We collected the blood samples of 60 patients who have been diagnosed with cancer. The DNA was extracted and the GSTM1 and GSTT1 genes were amplified using multiplex PCR. According to our research, the above two gene deletion is predominant among patients who have cancer. The results showed that from the total 60 patients GSTM1 and GSTT1 both deletions, GSTM1 gene deletion - 35%, GSTM1 gene deletion - 25%, GSTT1 gene deletion - 26.7%, GSTM1 and GSTT1 both positive -13.3 %. Therefore, we think that in order to prevent tumor and cancer, these gene mutations must be revealed and it is important to bring the risky group under medical control and assist them in order to prevent them from this disease.

P105 Glutathione S-transferase theta 1 protects against colitis through goblet cell differentiation via interleukin-22

Background The enzyme glutathione S-transferase theta 1 (GSTT1) is involved in detoxifying chemicals, including reactive oxygen species (ROS). Oxidative stress plays a key role in the pathogenesis of inflammatory bowel disease (IBD). Although mutation of the GSTT1 gene increases IBD susceptibility, the underlying mechanisms remain unexplained. Methods The Gstt1 gene was intrarectally or intraperitoneally delivered to mice with dextran sodium sulphate (DSS)-induced colitis. The GSTT1 gene was knocked down or knocked out using short interfering RNA or genome editing, respectively. Protein and mRNA expression and differentiation of goblet cells were evaluated. Results We identified decreased expression of GSTT1 in inflamed tissues from IBD patients and mice compared with their control counterparts, respectively. We also noted attenuation of colitis through gene transfer of Gstt1 to DSS-treated mice via the interleukin-22 (IL-22) pathway. GSTT1 was differently regulated by pathogens and host immune responses. Down-regulation of GSTT1 reduced innate defence responses and goblet cell differentiation. The GSTT1 mutation in intestinal epithelial cells as well as IBD patients diminished its dimerisation, which was connected to insufficient phosphorylation of signal transducer and activator of transcription 3 and p38/mitogen-activated protein kinase by their common activator, IL-22. Conclusion GSTT1 ameliorated IL-22 in colitis in a dependent manner and contributed as a modulator of goblet cells through sensing pathogens and host immune responses. Its mutations are linked to chronic intestinal inflammation due to its insufficient dimerisation. Our results provide new insights into GSTT1 mutations and their functional consequences in IBDs.