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The aim of this study was to test the hypothesis that glutathione- S-transferase (GST) genotypes were associated with COPD. GSTP1, GSTM1 and GSTT1 genotypes were determined by DNA methods and GST activity spectrophotometrically in older male Caucasian Croats (non- -smokers, ex-smokers, and smokers) with stable COPD (n = 30) and sex/age matched controls (n = 60). The distribution of GSTP1 genotypes and alleles in controls vs. COPD showed a statistical difference (p < 0.05). The odds ratio of CC/CT+TT (wild type GSTP1 exon 6 vs. joint heterozygous and mutant homozygous GSTP1 exon 6) was 10.000 and statistically different (p = 0.002). In this study, the GSTP1 mutant genotype of exon 5 (GG), as well as GSTP1 mutant and heterozygous genotypes of exon 6 (TT and CT), were suggested to be genetic contributors to COPD susceptibility. Null GSTM1, null GSTT1 and joint GSTM1/GSTT1 null genotypes were not disease associated. Serum GST was not associated with GST genotypes and COPD or smoking history in our study subjects. Conclusions drawn from the study should be further supported and clarified by studies with larger sample sizes.

Glutathione transferase P1-1 (GSTP1-1) is expressed in some human tissues and is abundant in mammalian erythrocytes (here termed e-GST). This enzyme is able to detoxify the cell from endogenous and exogenous toxic compounds by using glutathione (GSH) or by acting as a ligandin. This review collects studies that propose GSTP1-1 as a useful biomarker in different fields of application. The most relevant studies are focused on GSTP1-1 as a biosensor to detect blood toxicity in patients affected by kidney diseases. In fact, this detoxifying enzyme is over-expressed in erythrocytes when unusual amounts of toxins are present in the body. Here we review articles concerning the level of GST in chronic kidney disease patients, in maintenance hemodialysis patients and to assess dialysis adequacy. GST is also over-expressed in autoimmune disease like scleroderma, and in kidney transplant patients and it may be used to check the efficiency of transplanted kidneys. The involvement of GSTP in the oxidative stress and in other human pathologies like cancer, liver and neurodegenerative diseases, and psychiatric disorders is also reported. Promising applications of e-GST discussed in the present review are its use for monitoring human subjects living in polluted areas and mammals for veterinary purpose.

Background Although numerous treatment modalities exist for Prostate Cancer (PCa) with a complex pathophysiology, a significant worldwide health concern for males, early identification remains the paramount factor influencing disease prognosis. Proposed new biomarkers, including GSTP1, PTEN, and NKX3.1, may provide predictive and prognostic functions, hence enhancing the efficacy of PSA in diagnosing prostate cancer. Epigenetic variables associated with nutrition influence the blood gene expression levels of the new biomarkers GSTP1, PTEN, and NKX3.1. This study aimed to elucidate the correlation between nutrition-related epigenetic variables and the expression of the tumor suppressor genes GSTP1, PTEN, and NKX3.1 in benign prostate and prostate cancer patients. Methods This study was conducted with 41 newly diagnosed prostate cancer and 42 benign prostate patients, all aged 40 years and older. Participants had specific anthropometric measurements taken, and seven-day food records were kept. Serum levels of novel biochemical markers GSTP1, PTEN, and NKX3.1 were measured using an Enzyme-Linked Immunosorbent Assay (ELISA) method. Expression analyses of tumor-protective GSTP1, PTEN, and NKX3.1 genes were performed on prostate tissues obtained from fresh prostate biopsies taken from the groups and were associated with nutritional status. Results A significant relationship was found between the serum levels of GSTP1, PTEN, and NKX3.1, which are important in the formation and treatment of prostate cancer, and Gleason grade, tumor stage, and surgical margin status ( p  < 0.05). However, significant relationships were found between many macro and micronutrients obtained from the dietary pattern and effective in epigenetic pathways and GSTP1, PTEN, and NKX3.1 gene expressions ( p  < 0.05). Conclusions The findings of this investigation corroborated the notion that prospective novel markers, including GSTP1, PTEN, and NKX3.1, may serve predictive and prognostic functions in prostate cancer, hence enhancing the efficacy of PSA in its diagnosis. Dietary trends may influence the optimization of many epigenetic processes. Targeted therapeutic nutritional interventions designed to enhance gene expression will facilitate the formulation of prostate cancer prevention methods.

Background: Glutathione S-transferase 1 (GSTP1) inactivation is associated with CpG island promoter hypermethylation in the majority of prostate cancers (PCs). This study assessed whether the level of circulating methylated GSTP1 (mGSTP1) in plasma DNA is associated with chemotherapy response and overall survival (OS). Methods: Plasma samples were collected prospectively from a Phase I exploratory cohort of 75 men with castrate-resistant PC (CRPC) and a Phase II independent validation cohort ( n =51). mGSTP1 levels in free DNA were measured using a sensitive methylation-specific PCR assay. Results: The Phase I cohort identified that detectable baseline mGSTP1 DNA was associated with poorer OS (HR, 4.2 95% CI 2.1–8.2; P <0.0001). A decrease in mGSTP1 DNA levels after cycle 1 was associated with a PSA response ( P =0.008). In the Phase II cohort, baseline mGSTP1 DNA was a stronger predictor of OS than PSA change after 3 months ( P =0.02). Undetectable plasma mGSTP1 after one cycle of chemotherapy was associated with PSA response ( P =0.007). Conclusions: We identified plasma mGSTP1 DNA as a potential prognostic marker in men with CRPC as well as a potential surrogate therapeutic efficacy marker for chemotherapy and corroborated these findings in an independent Phase II cohort. Prospective Phase III assessment of mGSTP1 levels in plasma DNA is now warranted.

Considering the inadequacy of PSA measurement in the diagnosis of prostate cancer, it is aimed to establish a potential liquid biopsy diagnostic panel. 39 patients who underwent TRUS-biopsy and 15 healthy volunteers were included. Approximately 15 ml of venous blood samples taken from healthy volunteers and patients before biopsy were separated as plasma. Hypermethylation status of GSTP1 and RASSF1:RASSF2 genes was revealed in cfDNA materials collected from plasma samples. Correlation of this epigenetic change detected in PCa, BPH and healthy volunteer groups with pathology results was examined. Pathology reports of 39 patients included were 13 PCa, 3 ASAP, 3 HGPIN, and 20 BPH. In total, 3 of the patients with PCa had positive GSTP1, 4 had RASSF1 and 9 had positive RASSF2 methylation. It was seen that RASSF2 had the highest sensitivity (69%), specificity (39%) and NPV (80%), while RASSF1 had the highest PPV (30%). When the binary combinations of genes were examined it was observed that the GSTP1:RASSF1 combination had the highest sensitivity (46%), specificity (76%) and NPV (82%). When the methylation of all three genes was examined, it was observed that the sensitivity was quite low (8%), but the specificity (83%) increased significantly. Although we observed that the GSTP1 and RASSF1 methylation positivity rates that we examined in our study were higher in patients without prostate cancer, we found that the RASSF2 methylation rate was higher in patients with prostate cancer. randomized controlled studies are needed.

Preeclampsia, one of the leading causes of maternal and fetal morbidity and mortality, affects approximately 3–5% of pregnancies worldwide. However, its etiology remains poorly understood. The aim of this study was to identify molecular markers of preeclampsia. Protein concentrations in blood and urine were determined using the Bio-Plex Kidney Toxicity 1 assay Bio-Rad, Hercules, CA, USA followed by magnetic separation and flow cytometry. This study included 51 patients with preeclampsia and 25 healthy pregnant women. The results revealed that five out of the six serum biomarkers of kidney injury were elevated in the preeclampsia group compared to the control group (calbindin 1, clusterin, glutathione transferase pi (GSTP1), monocyte chemotactic protein 1 (MCP-1), and kidney injury molecule type 1 (KIM-1)). Additionally, the serum concentrations of calbindin 1, clusterin, GSTP1, and KIM-1 were significantly higher in both early-onset and late-onset preeclampsia compared to the control group. The analysis of urinary proteins showed that only the KIM-1 concentration was elevated in late-onset preeclampsia compared to the control group. These findings suggest that the calbindin 1, clusterin, GSTP1, KIM-1, and MCP-1 concentrations in maternal plasma could serve as potential biomarkers for monitoring kidney injury in preeclamptic women. This study provides a foundation for future research to explore novel biomarkers of preeclampsia and renal injury in pregnant women.

Recent research studies have shown that vitamin C (ascorbic acid) may affect bone mineral density and that a deficiency of ascorbic acid leads to the development of osteoporosis. Patients suffering from an inflammatory bowel disease are at a risk of low bone mineral density. It is vital to notice that patients with Crohn’s disease and ulcerative colitis also are at risk of vitamin C deficiency which is due to factors such as reduced consumption of fresh vegetables and fruits, i.e., the main sources of ascorbic acid. Additionally, some patients follow diets which may provide an insufficient amount of vitamin C. Moreover, serum vitamin C level also is dependent on genetic factors, such as SLC23A1 and SLC23A2 genes, encoding sodium-dependent vitamin C transporters and GSTM1, GSTP1 and GSTT1 genes which encode glutathione S-transferases. Furthermore, ascorbic acid may modify the composition of gut microbiota which plays a role in the pathogenesis of an inflammatory bowel disease.

A number of studies suggested that lead is related to the induction of oxidative stress, and alteration of immune response. In addition, modifying these toxic effects varied partly by GST polymorphism. The objectives of this study were to assess the association between the lead-induced alteration in serum hs-CRP, with GSTM1, GSTT1, and GSTP1 Val105Ile genetic variations and the health consequence from environmental lead exposure. The 924 blood samples were analyzed for blood lead, CRP, and genotyping of three genes with real-time PCR. Means of blood lead and serum hs-CRP were 5.45 μg/dL and 2.07 mg/L. Both CRP and systolic blood pressure levels were significantly higher for individuals with blood lead in quartile 4 (6.48–24.63 μg/dL) compared with those in quartile 1 (1.23–3.47 μg/dL, P<0.01). In particular, in men with blood lead >6.47 μg/dL the adjusted odds ratio (OR) of CRP levels for individuals with GSTP1 variants allele, GSTM1 null, GSTT1 null, double-null GSTM1, and GSTT1 compared with wild-type allele was 1.46 (95% CI; 1.05–2.20), 1.32 (95% CI; 1.03–1.69), 1.65 (95% CI; 1.17–2.35), and 1.98 (95% CI; 1.47–2.55), respectively. Our findings suggested that lead exposure is associated with adverse changes in inflammatory marker and SBP. GST polymorphisms are among the genetic determinants related to lead-induced inflammatory response.

Aberrant promoter methylation of genes is a common molecular event in breast cancer. Thus, DNA methylation analysis is expected to be a new tool for cancer diagnosis. In this article, we have established a new, high-performance DNA methylation assay, the one-step methylation-specific polymerase chain reaction (OS-MSP) assay, which is optimized for analyzing gene methylation in serum DNA. The OS-MSP assay is designed to detect aberrant promoter methylation of GSTP1, RASSF1A, and RARβ2 genes in serum DNA. Moreover, two quality control markers were designed for monitoring the bisulfite conversion efficiency and measuring the DNA content in the serum. Serum samples were collected from patients with primary ( n  = 101, stages I–III) and metastatic breast cancers ( n  = 58) as well as from healthy controls ( n  = 87). If methylation of at least one of the three genes was observed, the OS-MSP assay was considered positive. The sensitivity of this assay was significantly higher than that of the assay involving conventional tumor markers (CEA and/or CA15-3) for stages I (24 vs. 8%) and II (26 vs. 8%) breast cancer and similar to that of the assay involving the conventional tumor markers for stage III (18 vs. 19%) and metastatic breast cancers (55 vs. 59%). The results of the OS-MSP assay and those of the assay involving CEA and/or CA15-3 seemed to compensate for each other because sensitivity of these assays increased to 78% when used in combination for metastatic breast cancer. In conclusion, we have developed a new OS-MSP assay with improved sensitivity and convenience; thus, this assay is more suitable for detecting aberrant promoter methylation in serum DNA. Moreover, the combination of the OS-MSP assay and the assay involving CEA and/or CA15-3 is promising for enhancing the sensitivity of diagnosis of metastatic breast cancer.

Background. Uroplakins are glycoproteins investigated as potential markers of urothelial carcinoma. However, their role in chemical carcinogenesis is uncertain. In this study the diagnostic value of plasma and urine uroplakin IIIa (UPIIIa) levels in bladder cancer (BC) was investigated, particularly in the aspect of environmental exposure to chemical carcinogens, measured by DNA damage and detoxification ability in the BC smoking group. The correlation between uroplakin, 8-OHdG, and GSTπ was investigated. Material and Methods. This study included 61 BC patients and 33 healthy controls. UPIIIa, 8-OHdG, and GSTπ levels were estimated by the immunoenzymatic method (ELISA). Results. UPIIIa levels were elevated in BC patients in plasma (p≤0.001) and in urine (p≤0.001), as were 8-OHdG and GSTπ levels in urine. Moreover, the 8-OHdG level was higher in invasive or high grade tumors. A positive correlation between UPIIIa/GSTπ and 8-OHdG/GSTπ was observed, but no UPIIIa/8-OHdG correlation was noted. Conclusion. The study showed the diagnostic value of urine and plasma UPIIIa in BC (good sensitivity, specificity, and predictive value). The lack of UPIIIa correlation with 8-OHdG and smoking suggests that UPIIIa does not reflect the environmental exposure. The increased levels of 8-OHdG and GSTπ in the invasive tumor stage indicate their value in BC monitoring.