Lack of association of genetic polymorphisms of angiotensin-converting enzyme gene I/D and glutathione-S-transferase enzyme T1 and M1 with retinopathy of prematures

One of the most frequently observed causes of blindness in infancy is the pathogenesis known as retinopathy of prematurity (ROP). Angiotensin-converting enzyme (ACE) is a vital enzyme in the renin-angiotensin-aldosterone system; it is involved in the development of cardiovascular system diseases linked to I/D polymorphism of the ACE gene. Glutathione-S-transferase enzyme (GST) is one of the most important regulating components of the antioxidant system; there are indications that certain polymorphisms of GST genes (GSTT1, GSTM1), especially the null genotypes, increase the tendency for oxidative stress diseases. We investigated a possible correlation between ACE gene I/D and GSTT1 and GSTM1 gene polymorphisms in 56 prematures suffering from ROP and a control group composed of 48 prematures without ROP in a hospital in Turkey. PCR was used to detect the ACE I/D, GSTT1 and GSTM1 gene polymorphisms. Genotype was determined based on bands formed on agarose gel electrophoresis. We found no significant differences in genotype frequency of the ACE I/D, GSTT1 and GSTM1 genes between normal subjects and patients with ROP. Our results do not support an association of ACE I/D, GSTT1 and GSTM1 gene polymorphisms with risk for ROP.     

Glutathione S-transferase GSTM1, GSTT1 and p53 codon 72 polymorphisms in human tumor cells

The genes of the glutathione S-transferase (GST) family encode enzymes that appear to be critical in cellular protection against the cytotoxic effects, whereas p53 is a tumor suppressor gene. Despite a large number of studies on germline polymorphisms of GSTM1, GSTT1 and p53 genes, there have been very few reports on genotyping of these genes in human malignant tumor cells. In this study, we investigated GSTM1, GSTT1 and p53 codon 72 polymorphisms in a variety of human tumor cell lines originating from different organs to clarify tissue-specific polymorphic frequency of these genes in human solid tumors. The GSTM1 and GSTT1 genetic polymorphisms were evaluated using multiplex PCR techniques and PCR-RFLP analysis was conducted to identify p53 codon 72 genotypes. Gene expression of GSTM1 or GSTT1 was detected by RT-PCR in the cells with respective present genotype for each. Polymorphisms of p53 codon 72 detected by PCR-RFLP were also confirmed using SSCP and sequence analyses. GSTM1 and GSTT1 genotypes were various in 104 cell lines examined. Null GSTM1 genotype was dominant in small cell lung, kidney and ovarian carcinoma cells, whereas null GSTT1 genotype was dominant in cervical and endometrial carcinoma cells. GSTM1 and GSTT1 genotypes in ovarian carcinoma cells were quite similar to those in small cell lung carcinoma cells. Polymorphic frequency of p53 codon 72 was also various among the cells, however, the Pro allele was found in only 1 of 6 kidney, 14 cervical and 4 endometrial carcinoma cell lines. There was a significant difference in GSTM1 and p53 genotypes between 34 small cell and 24 non small cell lung carcinoma cells (P < 0.01). Combined study on the distribution of GSTM1, GSTT1 and p53 genotypes revealed that null GSTM1 genotype was associated with the Arg allele of p53 codon 72 in 58 lung carcinoma cells and null GSTT1 genotype was associated with the Pro/Pro homozygote in 104 tumor cell lines examined. This is the first study examining GSTM1, GSTT1 and p53 codon 72 polymorphisms in a variety of human solid tumor cells and suggesting that polymorphic frequency of these genes may be tissue- and organ-specific. The molecular interaction between GST gene defects and p53 codon 72 genotype in the development of human malignant tumors should be further investigated.     

Glutathione S-transferase M1, T1 and P1 genetic polymorphisms, cigarette smoking and gastric cancer risk

Glutathione S-transferases (GSTs) belong to a superfamily of detoxification enzymes that provide critical defences against a large variety of chemical carcinogens and environmental toxicants. GSTs are present in most epithelial tissues of the human gastrointestinal tract. We investigated associations between genetic variability in specific GST genes (GSTM1, GSTT1 and GSTP1), the interaction with cigarette smoking and susceptibility to gastric cancer. The GSTM1, GSTT1 and GSTP1 polymorphisms were determined using real-time polymerase chain reaction (PCR) and fluorescence resonance energy transfer with Light Cycler Instrument. The study included 70 patients with gastric cancer and 204 controls. Associations between specific genotypes and the development of gastric cancer were examined by use of logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). The GSTM1 homozygous null genotype was associated with an increased risk of developing gastric cancer (OR = 1.73; 95% CI = 1.10-3.04). GSTT1 homozygous null genotype and GSTP1 genotypes were not associated with the risk of gastric cancer. Also there was no difference between cases and controls in the frequency of val-105 and ile-105 alleles (p = 0.07). After grouping according to smoking status, GSTM1 null genotype was associated with an increased gastric cancer risk for smokers (OR = 2.15; 95% CI, 1.02-4.52). There were no significant differences in the distributions of any of the other GST gene combinations. Our findings suggest that the GSTM1 null genotype may be associated with an increased susceptibility to gastric cancer.     

Glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) polymorphisms in a sample of the population in Northern Italy

Glutathione S-transferase is a group of multifunctional enzymes important in the metabolism of xenobiotics. GSTT1 and GSTM1 are polymorphic in human populations. Since a relation between polymorphism and cancer susceptibility has been found, their distribution in human populations is of great interest. In the present study the distribution of GSTT1 and GSTM1 genotypes was studied in a total sample of 252 individuals of three localities of north-west Italy (Postua, Cavaglià and Biella) by PCR test. The frequencies of GSTT1 and GSTM1 "null" genotypes were respectively 7.94% and 34.92%. There are no significant differences between the populations studied in the GSTT1 "null" genotypes. On the other hand, for GSTM1 the frequency of gene deletion in Postua (25.5%) differs significantly (p < 0.01; chi-square test) from that of Biella (46.32%), which approaches the values indicated by most studies for Europeans (about 50%). The analysis of the frequencies of GSTT1 and GSTM1 polymorphisms among different age groups showed a lower frequency of negative genotypes in the older group, although not statistically confirmed.     

Glutathione-S-transferase and microsomal epoxide hydrolase polymorphism and viral-related hepatocellular carcinoma risk in India

Hepatocellular carcinoma (HCC) is the fourth most common cancer worldwide, the main etiological factors being chronic infections with hepatitis B and C viruses. Genetic polymorphic forms of glutathione-S-transferase (GST) and microsomal epoxide hydrolase (mEPHX) have been associated with risk for various malignancies. The present study was undertaken to evaluate the association of GSTT1 and GSTM1 null genotypes and mEPHX polymorphisms with hepatitis virus-related HCC risk in an Indian population. Three groups of subjects were considered, control (n = 169), chronic viral hepatitis (n = 174), and HCC (n = 63). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for this polymorphic study. Genotype distributions between categories were compared using the chi2 test; odds ratios (ORs) and 95% confidence interval were calculated to express the relative risk. GSTT1 null genotype was associated with 2.23-fold (p < 0.05) increased risk for HCC development as compared to the control group. However, GSTM1 null genotype was found to have a protective effect when hepatitis patients were considered. In case of mEPHX, R139R imposed a risk factor for HCC with both control (OR = 1.81) and chronic hepatitis-infected (OR = 2.06) subjects. Combination of heterozygous mutant genotypes at mEPHX exons 3 and 4 revealed a twofold risk (nonsignificant) for HCC. Further, combination of GSTM1 and T1 genotypes with either of exon 3 or 4 polymorphism of mEPHX displayed synergistic associations (risk or protective) for HCC development. GST and mEPHX variants share a positive association with viral-related HCC risk in Indian population, although a larger sample size is still required to confirm the results.     

南京地区青年乳腺癌患者GSTM1、GSTT1 基因多态性与易感性 的初步研究

目的:研究GSTM1、GSTT1基因多态性与乳腺癌遗传易感性的关系。方法:应用PCR技术检测乳腺癌组和对照组人群GSTM1和GST T1基因。结果:GSTM 1和GSTT 1基因缺失率在乳腺癌组分别为63.4%(59/93)和54.8%(51/93),对照组分别为39.3%(35/89)和33.7%(30/89),两组比较,差异有统计学意义(P<0.01或P<0.05)。结论:GSTM1和GST T1缺失为乳腺癌遗传易感因素。     

Impact of glutathione-S-transferase gene polymorphisms on enzyme activity, lung function and bronchial asthma susceptibility in Egyptian children

Background

Asthma is a complex multifactorial disease with an obvious genetic predisposition. Polymorphisms of the glutathione-S-transferase (GST) genes are known risk factors for some environmentally-related diseases. The aim of the present study was to investigate the role of polymorphisms in the GSTT1, GSTM1 and GSTP1 genes and asthma susceptibility in Egyptian children, and to analyze their effect on GST activity and lung function.

Methods

GSTT1 and GSTM1 gene polymorphism was genotyped using the multiplex polymerase chain reaction (PCR) and GSTP1 ILe105Val polymorphism was determined using PCR-restriction fragment length polymorphism (PCR-RFLP) in 168 healthy and 126 asthmatic children (82 atopic and 44 nonatopic). Also GST enzyme activity and lung function were evaluated.

Results

Asthmatic children had a significant higher prevalence of the GSTM1 null (P = 0.003) and significant lower prevalence of GSTP1 Val/Val genotypes (P = 0.02) than control group. Lung function was significantly decreased in GSTM1 null genotype and GSTP1 Ile/Ile genotype. GSTP1 Val/Val genotypes and GSTM1 null genotype had a significant decrease in plasma GST activity.

Conclusions

GST genes polymorphisms may play an important role in pathogenesis and susceptibility to asthma in children.     

GSTT1 and GSTM1 gene polymorphisms in European and African populations

Glutathione S-transferases (GSTs) are a superfamily of detoxificant enzymes. Pharmacogenomic studies have revealed interethnic differences in GST allelic frequencies. This study is focused on GSTT1 (gene deletion, rs17850155, rs2234953, and rs11550605) and GSTM1 (gene deletion) gene frequency distributions in two population samples of Europe origin (Italy, n = 120; Spain, n = 94) and two population samples of Africa origin (Cameroon, n = 126; Ethiopia, n = 153). Detection of GSTT1 and GSTM1 null genotypes was performed by multiplex PCR analysis, while the other GSTT1 gene polymorphisms were detected using allele specific PCR and sequencing. GSTT1 and GSTM1 null frequencies in the samples analyzed fit with the variability range observed in European and African populations, respectively. The SNP analysis in GSTT1 gene did not highlight any nucleotide substitution in 493 individuals analyzed. The comparisons among GSTM1 and GSTT1 null phenotype frequencies in worldwide populations show different patterns between Asians, Africans, and Europeans. Important insights into the effects of GSTM1 and GSTT1 gene deletions on the pathogenesis of human diseases have been hypothesized. Detailed studies on the geography of GST variants could therefore increase knowledge about the relationship between ethnicity and the prevalence of certain diseases.     

Relation of glutathione S-transferase T1, M1 and P1 genotypes and breast cancer risk

The aim of this study was to investigate associations between genetic variability in specific Glutathione S-transferases (GST) genes (GSTM1, GSTT1 and GSTP1) and susceptibility to breast cancer. Genotypes of blood specimen DNA were determined for 65 women with incident cases of breast cancer and 108 control subjects. Associations between specific genotypes and the development of breast cancer were examined by the use of logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Neither GSTT1 nor GSTM1 homozygous null genotype was associated with a significant increased risk of developing breast cancer. The presence of valine alleles compared to isoleucine alleles in codon 105 in GSTP1 did not increase the risk of breast cancer development. The risk of breast cancer associated with a combined GSTT1 and GSTM1 null genotype was 3.37 (95% CI = 0.76-2.95, p = 0.115). The only significant association between increased risk of breast cancer development and GSTs polymorphisms was found when GSTT1 null, GSTM1 null and the presence of valine in GSTP1 in codon 105 were combined (p < 0.048, OR = 3.75, 95% CI = 1.01-13.90). Our findings suggest that combined genetic variability in members of the GST gene family may be associated with an increased susceptibility to breast cancer.     

Glutathione S-transferase variants as risk factor for essential hypertension in Italian patients

Involvement of genetic polymorphisms in arterial hypertension has already been reported, including GST genes, with contrasting results. The present research evaluates the possible association between GST gene polymorphisms and essential hypertension (EH) in an Italian population sample. 193 hypertensive subjects and 210 healthy controls were recruited. Buccal cells were collected from each subject using an oral swab and DNA was extracted using the phenol:chloroform:isoamilic alcohol method. GST SNPs were determined using the PCR-RFLP method, while GST null polymorphisms were determined using a Multiplex PCR. Among GST polymorphisms, only the frequency of the GSTT1 null phenotype was significantly higher in hypertensive patients than in normotensive participants. GSTT1 null individuals were significantly associated with increased risk of hypertension [P < 0.001; adjusted OR 2.24 (1.43-3.50)]. In sex-based analysis, the risk was significantly higher in female hypertensives [P < 0.001; adjusted OR 3.25 (1.78-5.95)] but not in male subjects. This study analyzed all GST gene that, in other research, have been studied in relation to arterial hypertension and the GSTO polymorphisms, showing an association only with GSTT1. The results for the GSTO genes represent the first analysis of this GST class in relation to blood pressure regulation. The association between the GSTT1 null phenotype and EH was confirmed in the overall population and in women, but not in men. These data suggest that GSTT1 could be a sex-specific candidate gene for EH.     

GSTM1, GSTT1 and CYP1A1 detoxification gene polymorphisms and susceptibility to smoking-related coronary artery disease: a case-only study

Cigarette smoking is a powerful risk factor for coronary artery disease (CAD), leading to the formation of DNA alterations within blood vessels and heart. However, the degree of smoking-related atherosclerosis varies from individual to individual. Genetic polymorphisms of relevant xenobiotic metabolising enzymes may determine the susceptibility of an individual response to environmental toxicants. The purpose of this study was to test the hypothesis that the inheritance of polymorphic genes encoding cytochrome P450 1A1 (CYP1A1 MspI) and glutathione S-transferases (GSTM1(null) and GSTT1(null)) may be causally associated with the presence and severity of smoking-induced CAD. In a case-only design, 222 (179 male, 57.8+/-10.3 years) consecutive smoker patients who had undergone elective and diagnostic coronary angiography were recruited. We found a group (n=169) of smoker patients with significant CAD, defined as>50% reduction in diameter of at least one major vessel, and a group without obstructive CAD (n=53). No significant differences were observed in CYP1A1 genotypes frequencies between CAD and non-CAD smokers (p=0.1). Homozygous deletion of GSTM1 had a frequency of 58.6% among patients with CAD and 45.3% among those without CAD (p=0.08). The frequency of the GSTT1(null) genotype was 43.8% among the patients with CAD and 24.5% among CAD-free subjects (p=0.01). After adjustment for traditional risk factors, the presence of combined GSTM1(null)GSTT1(null) genotypes was significantly associated with an increased risk of CAD (OR=3.9; 95% CI: 1.3-11.4, p=0.01). Moreover, smokers with combined GSTM1(null)GSTT1(null) genotypes had significantly higher number of stenosed vessels than those with the positive genotype (2.3+/-0.9 versus 1.7+/-0.8, p=0.03). Our findings showed that smokers carrying GST deleted genotypes have an increased susceptibility to the smoking related coronary artery disease. Exploring gene-smoking effect provides an excellent model in order to understand gene-environment toxicants interaction and its implications to cardiovascular disease.     

Genetic variants of glutathione S-transferase and the risk of acute myeloid leukemia in a Saudi population

ObjectiveThis study aims to investigate the genetic association of acute myeloid leukemia and glutathione S-transferase (GST) gene polymorphisms in a Saudi population.Method100 AML cases and 100 healthy controls were recruited from the Riyadh regional hospital. In the GST gene, GSTM1 and GSTT1 variants were genotyped by multiplex PCR, and GSTP1 variants were genotyped by PCR-RFLP analysis. Statistical analysis between AML cases and controls included anthropometric measurements and evaluation of the genotypic and allelic frequencies.ResultThe null genotypes of GSTM1 and GSTT1 showed no association with AML [OR 0.56 (0.26–1.19); p = 0.31 and OR 0.65 (0.37–1.16); p = 0.14]. Similarly, the GSTP1 genotype and allele frequencies did not indicate any association with AML [GG + AG vs. AA: OR 0.75 (0.43–1.31) and p = 0.32; GG vs. AA: OR 1.73 (0.55–5.44) and p = 0.34; G vs. A: OR 0.95 (0.61–1.46) and p = 0.82]. Further, a haplotype analysis between AML cases and controls did not show any positive association (p < 0.05).ConclusionIn conclusion, there was no statistical association of the genotypes and alleles in GSTM1, GSTT1, and GSTP1 with AML. Our results confirm the negative association of the investigated genetic markers with susceptibility to AML. Further association studies would be required in different ethnic populations to facilitate a meta-analysis in the future. Our findings suggest that the GST gene has no role in the pathogenesis of AML in patients from Saudi Arabia.     

Glutathione S-Transferase M1 (GSTM1) and T1 (GSTT1) Null Polymorphisms and the Risk of Hypertension: A Meta-Analysis

Background

Some studies have recently focused on the association between glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms and hypertension; however, results have been inconsistent.

Objective

In order to drive a more precise estimation, the present systematic review and meta-analysis is performed to investigate the relationship between the GSTM1 and GSTT1 null polymorphisms and hypertension.

Methods

Eligible articles were identified by a search of several bibliographic databases for the period up to August 17, 2013. Odds ratios were pooled using either fixed-effects or random-effects models.

Results

Regarding the GSTM1 null/present genotype, 14 case—control studies were eligible (2773 hypertension cases and 3189 controls). The meta-analysis revealed that it might present a small increased risk for hypertension, although the effect was not statistically significant (odd ratio (OR) = 1.16, 95% confidence interval (CI): 0.96, 1.40; P = 0.002, I2 = 59.8%). Further subgroup analysis by ethnicity and control source suggested that the association was still not significant. Thirteen case—control studies were eligible for GSTT1 (2497 hypertension cases and 3078 controls). No statistically significant association was observed between the GSTT1 null genotype and hypertension risk (OR = 1.14, 95% CI: 0.85, 1.53; P = 0.000, I2 = 80.3%). Furthermore, stratification by ethnicity and control source indicated no association between the GSTT1 null genotype and hypertension risk. We further confirmed the association by sensitivity analysis. No publication bias was detected.

Conclusion

This meta-analysis suggests that the GSTM1 and GSTT1 null polymorphisms are not associated with the risk of hypertension. Future large well-designed epidemiological studies with individual information, lifestyle factors, and environmental factors are warranted to validate the present findings.     

Trimodal GSTT1 and GSTM1 genotyping assay by real-time PCR

The GSTT1 and GSTM1 genes are characterized by the existence of a GST*0 null allele responsible for a lack of enzyme activity, with the respective null genotypes GSTT1*0/0 and GSTM1*0/0. The three resulting genotypes (GSTs*1/1, *1/0 and *0/0) are associated with a trimodal distribution of glutathione-conjugator activity. Previous epidemiological studies have only evaluated the cancer risk associated with the GST null genotype relative to the two GST carrier genotypes (GSTs1*1/1 and *1/0). We developed GSTT1 and GSTM1 TaqMan real-time quantitative PCR assays to discriminate each of the three genotypes, with the albumin gene (ALB) as reference. The mean N(GSTT1*1/1) value was 1.0 (95% confidence interval 0.80-1.20). The mean N(GSTT1*1/0) value was 0.48 (95% CI 0.36-0.60). One (3.4%) of the 29 DNA samples yielded the GSTM1*1/1 genotype (N(GSTM1*1/1) = 1), a frequency in keeping with the Hardy-Weinberg distribution. The mean N(GSTM1*1/0) value was 0.50 (95% CI 0.42-0.58). All GSTT1*0/0 and GSTM1*0/0 samples yielded N(GST) values of 0 (Ct = 40); the frequencies of these genotypes (27.6% and 55.2%, respectively) were in keeping with published data. The GSTT1 and GSTM1 real-time PCR assays described here unambiguously discriminate each of the three existing genotypes which should be valuable for assessing the relative risk of cancer associated with each of the three GST genotypes.     

Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case–control study

Oxidative stress and xenobiotic metabolizing enzymes are suspected to be related to carcinogenesis by different cellular mechanisms. Hence, our study aimed at identifying potential relationships between antioxidant defense parameters measured in blood and glutathione S-transferase (GST) genetic polymorphisms of four GST izoenzymes in lung cancer patients and reference individuals. The case-control study included 404 lung cancer patients and 410 non-cancer subjects as controls, matched by age, gender and place of living (central Poland). In control subjects with GSTM3*A/*A, GSTT1 null, GSTM1 null + GSTT1 null, GSTM3*A/*A + GSTT1 null genotype, glutathione peroxidase activity was significantly higher (P < 0.05) than in controls possessing respective potential protective GST genotypes. Controls with GSTM3*A/*A + GSTP1*B genotype presented significantly higher ceruloplasmin activity (P < 0.05) than GSTM3*B + GSTP1*A/*A carriers. Zinc level was significantly higher (P < 0.05) in controls and cases with GSTP1*B + GSTT1 null genotype and in cases with GSTM1 null + GSTP1*B genotype, when compared with respective potential protective GST genotypes. This case-control study indicates that particular defective GST genotypes may enhance the defense against oxidative stress. The potential relationship between the investigated antioxidative enzymes and microelements, and common functional genetic polymorphism of GST was observed mostly in control subjects.     

Glutathione S-transferase gene polymorphisms in Turkish patients with diabetes mellitus

Glutathione S-transferases (GSTs) are enzymes involved in the metabolism of many disease-causing electrophilic substrates and protect the cells against oxidative stress. In the present study, we investigated the GSTM1, GSTT1 and GSTP1 gene polymorphisms in diabetic patients and healthy individuals and searched whether polymorphisms in GST genes are associated with diabetes mellitus (DM) in the Turkish population. The study population consisted of 98 unrelated healthy individuals and 98 patients with DM. Genotyping of GSTM1, GSTT1 and GSTP1 genes was performed using real time polymerase chain reaction with a Light Cycler instrument. Patients had a higher frequency of the GSTM1 null genotype than the control group (Odds ratios, OR = 3.7; 95% confidence intervals, CI = 2.05-6.70). However, there was no significant difference in the frequencies of the GSTT1 and GSTP1 gene polymorphisms between the patients and control group. The combined analysis of these three GST genotypes showed a further DM risk increase (OR = 5.7, 95% CI = 1.51-31.07). This is the first study to determine the association of diabetes with GST gene polymorphism in the Turkish population. These results show that GSTM1 null genotype may play a significant role in the aetiopathogeneses of DM and the GSTM1 gene may be a useful marker in the prediction of DM susceptibility of the Turkish population.     

Polymorphisms of methylenetetrahydrofolate reductase and glutathione S-transferase are not associated with the risk of papillary thyroid cancer in Korean population

Korea has the highest incidence of thyroid cancer of any nation. We conducted a population-based, case–control study of the association between the risk of papillary thyroid cancer (PTC) in the Korean population and polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T, glutathione S-transferase class mu (GSTM1), and glutathione S-transferase class theta (GSTT1). The study subjects consisted of 2,194 newly diagnosed PTC cases and 1,669 population-based healthy controls. Odds ratios adjusted by age, sex, body mass index, smoking, drinking, serum thyroid-stimulating hormone level, family history of thyroid cancer, and previous history of thyroid disease, with 95 % confidence intervals, were estimated using logistic regression analysis. The frequencies of MTHFR 677TT genotypes, and null genotypes of GSTM1 and GSTT1 were 19.2, 56.8, and 51.4 % among PTC cases and 17.4, 54.1, and 50.6 % among the controls, respectively. No significant associations between PTC and TT genotypes of MTHFR C677T, null genotypes of GSTM1 and GSTT1, or double-null (GSTM1-GSTT1) genotypes were found. These findings suggest that polymorphisms of the MTHFR C677T, GSTM1 and GSTT1 genotypes do not contribute to the development of PTC susceptibility in the Korean population.     

Glutathione S-transferase M1, T1 and P1 polymorphisms and bladder cancer risk in Egyptians

Previous studies suggest that bladder cancer risk may vary with GST genotype but these results are inconsistent. The aim of this study was to explore whether GSTM1, GSTT1 and GSTP polymorphisms were associated with increased bladder cancer risk in an Egyptian population. GSTM1, GSTT1 and GSTP1 genotype frequencies were determined in bladder cancer cases (n=72) and healthy controls with no history of malignancies (n=82) using PCR-based techniques. The GSTT1*2 genotype was particularly associated with increased risk (OR 2.71, 95%CI 1.27-5.73) and the GSTM1*2 genotype to a lesser extent (OR 1.63, 95%CI 0.85-3.10). 18.1% of cases but only 7.3% of controls were GSTP1*B*B homozygotes (OR 2.38, 95%CI 0.83-6.87). The presence of two or more a priori at-risk genotypes was associated with increased bladder cancer risk (OR 2.42; 95%CI 1.47-3.97). These results suggest that polymorphisms in the GST genes are associated with increased risk of bladder cancer among Egyptians.     

Effects of glutathione S-transferase T1 and M1 deletions on advanced carotid atherosclerosis, oxidative, lipid and inflammatory parameters

Glutathione S-transferases (GSTs) carry out a wide range of functions in cells, such as detoxification of endogenous compounds, removal of reactive oxygen species, and even catalysis of reactions in metabolic pathways beyond detoxification. Based on previous research, GSTM1 and GSTT1 might modify the risk of atherosclerosis. The aim of our study was to analyze the possible association of GSTM1 and GSTT1 gene polymorphisms with the occurrence of carotid plaque (CP); and biochemical parameters of oxidative stress, lipid profile and inflammation, in 346 consecutive patients with advanced atherosclerosis that underwent endarterectomy. A multiplex polymerase chain reaction (PCR) method was used to detect the deletions in GSTM1 and GSTT1 genes in the genomic DNA in 346 patients and 330 controls. The adjusted OR for CP presence (adjusted for age, gender, smoking, hypertension, BMI, HDLC, TG) was 0.24, 95 %CI 0.08–0.7, p < 0.01 for GSTT1 null and 1.13, 95 %CI 0.62–2.07, p = 0.7 for GSTM1 null genotype. We found significantly lower plasma lipoprotein (a) (Lp(a)) levels in GSTT1 null compared to wild-type genotype carriers in patient group (20.68 ± 26.02 mg/dl vs. 40.66 ± 42.89 mg/dl, mean ± SD, p = 0.04). The serum interleukin-6 (IL-6) values were significantly influenced by both GST polymorphisms in patients with CP. Our results, showing the significant reduction of GSTT1 deletions in patients with CP, suggest involvement of GSTs in carotid atherosclerosis. This study shows additional view of the possible role of GSTs in advanced chronic inflammatory disease of vascular system, but the confirmation in a larger studies in different populations are needed.     

Glutathione S-Transferase M1, T1, P1 Genotypes and Risk for Development of Colorectal Cancer

The glutathione S-transferase (GST) supergene family is an important part of cellular enzyme defense against endogenous and exogenous chemicals, many of which have carcinogenic potential. The present investigation was conducted to detect a possible association between polymorphisms at the GSTM1, GSTT1, and GSTP1 genes and the interaction with cigarette smoking and colorectal cancer incidence. We examined 181 patients with colorectal cancer and 204 controls. DNA was extracted from whole blood, and the GSTM1, GSTT1, and GSTP1 polymorphisms were determined using a real-time polymerase chain reaction and fluorescence resonance energy transfer with a Light-Cycler instrument. Associations between specific genotypes and the development of colorectal cancer were examined by use of logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI). The GSTM1 polymorphism was associated with an increased risk of developing colorectal cancer (OR = 1.62, 95% CI: 1.06–2.46). Also the risk of colorectal cancer associated with the GSTT1 null genotype was 1.64 (95% CI: 1.10–2.59). Statistically no differences were found between patients with colorectal cancer and control groups for the GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes. In addition, the frequencies of the GSTM1 and GSTT1 deletion genotypes differed significantly between the cases and controls for current smokers; the GSTT1 null genotype especially is associated with a greater risk of colorectal cancer (OR = 2.44, 95% CI: 1.24–4.81). The GSTM1 and GSTT1 deletions were associated with an increased risk of developing a transverse or rectal tumor (OR = 1.86, 95% CI: 1.15–3.00; OR = 1.70, 95% CI: 1.02–2.84; respectively). The glutathione S-transferase polymorphisms were not associated with risk in patients stratified by age. The risk of colorectal cancer increased as putative high-risk genotypes increased for the combined genotypes of GSTM1 null, GSTT1 null, and either GSTP1 valine heterozygosity or GSTP1 valine homozygosity (OR = 2.69, 95% CI: 1.02–7.11). In conclusion, the results obtained in this study clearly suggest that those susceptibility factors related to different GST polymorphic enzymes are predisposing for colorectal cancer.