GSTM1), T1 Research Articles

A study of the association of glutathione S-transferase M1/T1 polymorphisms with susceptibility to vitiligo in Egyptian patients

BackgroundThe association of glutathione S-transferases M1/T1 (GSTM1/T1) null polymorphisms with vitiligo was proposed in several studies including two Egyptian studies with contradictory results.ObjectiveThe aim here was to assess the association between GSTM1/T1 null polymorphisms and the susceptibility to vitiligo in a larger sample of Egyptian patients with generalized vitiligo.MethodsThis study included 122 vitiligo patients and 200 healthy controls that were age, and gender matched. Assessment of GSTM1/T1 gene polymorphisms was done using a multiplex polymerase chain reaction (PCR).ResultsIncreased odds of generalized vitiligo was observed with the null genotypes of GSTM1 and GSTT1 polymorphisms (P<0.05). Controls with GSTM1 null/GSTT1+ heterozygosis presented with a 2.97 odds protection from having generalized vitiligo (OR=2.97, 95%CI=1.1-7.7) (P=0.02) compared with patients.Study LimitationsSmall sample size of patients.ConclusionsThis study showed a significant trend towards an association with the combination of the GSTM1/GSTT1 double null polymorphism and generalized vitiligo. Individuals with GSTM1 null/GSTT1+ heterozygosis have a 2.97 odds protection from having generalized vitiligo compared with patients. It was is the first time, to our knowledge, that such an association has been reported.

Association between glutathione S-transferases M1, T1 and P1 gene polymorphisms and prostate cancer in Koreans

Prostate cancer (PCa) is the most commonly diagnosed cancer in the developed world, and the incidence of this cancer is rising rapidly in many countries. Several polymorphic genes encoding enzymes involved carcinogenesis have been studied as potential risk factor of prostate cancer. Genetic polymorphisms in glutathione S-transferases M1 (GSTM1), T1 (GSTT1) and P1 (GSTP1) genes have been constantly reported to have a meaningful effect on prostate cancer risk. But other surveys of this relationship have yielded inconsistent results. To assess the possible contribution of the GSTM1, GSTT1, and GSTP1 gene polymorphisms in prostate cancer, we performed a population-based study of 139 prostate cancer patients and 115 healthy controls based on their genotype distributions of the genes. There were no differences in distributions of genotype frequencies of GSTM1 and GSTP1 polymorphisms between prostate cancer patients and controls (OR 1.60, 95 % CI 0.886–2.860 for GSTM1 and OR 1.38, 95 % CI 0.739–2.577 for GSTP1). In contrast, the distribution of GSTT1-null genotype is significantly different between the prostate cancer case and controls (OR 0.26, 95 % CI 0.128–0.518, p < 0.001). Meanwhile, GSTP1 I/V and V/V genotypes were significantly associated with prostate cancer where the PSA level was more than 10.0 (OR 2.73, 95 % CI 1.319–5.639, p = 0.006). Thus, our data imply that the GSTT1-null genotype may not be a risk factor but a protective factor of prostate cancer and GSTP1 Val allele is a risk factor for the prostate cancer where the PSA level was high, although functional studies with larger sample size are necessary to elucidate these findings.

The null polymorphism of the GSTM1/T1 gene is not associated with susceptibility to systemic lupus erythematosus: a meta-analysis.

Previous studies have suggested that the null polymorphism of the glutathione S-transferases M1/T1 (GSTM1/T1) gene may be associated with the risk of developing systemic lupus erythematosus (SLE). We further explored this potential association using a meta-analysis. A systematic literature search was carried out in the scientific literature databases and we used odds ratios (OR) and 95 % confidence intervals (CIs) to evaluate the strength of this association. All statistical analyses were calculated using Stata software 11.0, and Bonferroni correction was used to adjust the p values. Nine eligible articles with 1,850 patients and 2,826 controls were identified. Our results showed the null polymorphism of the GSTM1 gene was associated with SLE in East Asians (OR 1.32, 95 % CI 1.04-1.69, p = 0.024), but not in Europeans and Africans. However, when Bonferroni corrections were applied (p = 0.05/2 = 0.025), we could not be sure of this association. We further analysed the associations between the GSTT1 gene null polymorphism and the risk of SLE. The results of this investigation showed that this null polymorphism was not associated with susceptibility to SLE in all included populations. In conclusion, the null polymorphism of GSTM1/T1 gene may not be associated with the risk of SLE. More studies are needed to confirm this lack of association between key oxidative defense genes and susceptibility to SLE in the future.

Glutathione s-transferase M1 and T1 genetic polymorphisms in Iranian patients with glaucoma.

Glaucoma is the second leading cause of blindness and it is related to oxidative stress based on numerous studies. Glutathione S-transferases (GSTs) are members of multigenic family, which have important role in cells as an antioxidant. In the present study, we examined the polymorphism of GSTT1 and GSTM1 deletion genotypes (T0M1, T1M0, and T0M0) in 100 Glaucoma patients (41with primary open angle glaucoma (PCAG), and 59 with primary closed angle glaucoma (POAG)) compared to 100 healthy subjects. GSTM1and GSTT1 polymorphisms were determined by multiplex polymerase chain reaction. GSTM1 and GSTT1 null deletions genotypes were determined in 22 (53.7%) and 7 (17.1%) patients with PCAG and 34 (34%) and 15 (15%) in healthy subjects. Comparison between patients and healthy subjects regarding GSTM1 and GSTT1 genotypes revealed increase of GSTM1 null deletions genotypes in patients with PCAG (P=0.03). It was concluded that the increased frequencies of GSTM1 null in patients with PCAG could be a risk factor for incidence of PCAG in the Iranian population.

The Incidence of Liver Injury in Uyghur Patients Treated for TB in Xinjiang Uyghur Autonomous Region, China, and Its Association with Hepatic Enzyme Polymorphisms NAT2, CYP2E1, GSTM1 and GSTT1

Background and ObjectiveOf three first-line anti-tuberculosis (anti-TB) drugs, isoniazid is most commonly associated with hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, NAT2, CYP2E1, GSTM1and GSTT1, that code for drug-metabolizing enzymes. This study evaluated whether the polymorphisms in these enzymes were associated with an increased risk of anti-TB drug-induced hepatitis in patients and could potentially be used to identify patients at risk of liver injury.Methods and DesignIn a cross-sectional study, 2244 tuberculosis patients were assessed two months after the start of treatment. Anti-TB drug-induced liver injury (ATLI) was defined as an ALT, AST or bilirubin value more than twice the upper limit of normal. NAT2, CYP2E1, GSTM1 and GSTT1 genotypes were determined using the PCR/ligase detection reaction assays.Results2244 patients were evaluated, there were 89 cases of ATLI, a prevalence of 4% 9 patients (0.4%) had ALT levels more than 5 times the upper limit of normal. The prevalence of ATLI was greater among men than women, and there was a weak association with NAT2*5 genotypes, with ATLI more common among patients with the NAT2*5*CT genotype. The sensitivity of the CT genotype for identifying patients with ATLI was 42% and the positive predictive value 5.9%. CT ATLI was more common among slow acetylators (prevalence ratio 2.0 (95% CI 0.95,4.20) )compared to rapid acetylators. There was no evidence that ATLI was associated with CYP2E1 RsaIc1/c1genotype, CYP2E1 RsaIc1/c2 or c2/c2 genotypes, or GSTM1/GSTT1 null genotypes.ConclusionsIn Xinjiang Uyghur TB patients, liver injury was associated with the genetic variant NAT2*5, however the genetic markers studied are unlikely to be useful for screening patients due to the low sensitivity and low positive predictive values for identifying persons at risk of liver injury.

Association of glutathione S-transferase M1/T1 polymorphisms with susceptibility to vitiligo

BackgroundSome studies suggested that Glutathione S-transferases M1/T1(GSTM1/T1) null polymorphisms may be associated with the risk of vitiligo. AimsThe purpose of this study is to further evaluate the association between GSTM1/T1 null polymorphisms and the susceptibility to vitiligo. MethodsWe carried out a retrieval of studies in the databases. Odds ratios (OR) and 95% confidence intervals (95% CIs) were used to assess the strength of this association. We analyzed the data using Stata 11.0. ResultsSix case–control studies including 1358 cases and 1673 controls were included in this meta-analysis. Our overall results showed the GSTM1 or GSTT1 null polymorphism was associated with vitiligo (GSTM1:OR=1.59, 95% CI: 1.21–2.08, P=0.001; GSTT1: OR=1.30, 95% CI: 1.12–1.51, P=0.001). In the subgroup analysis, the GSTM1 null polymorphism might be a genetic risk factor to vitiligo in East Asian (OR=1.71, 95% CI: 1.12–2.63, P=0.014) but not in the Mediterranean, however individuals with the GSTT1 null polymorphism in the Mediterranean (OR=1.76, 95% CI: 1.15–2.71, P=0.010) but not in East Asian have a greater predisposition to vitiligo. In addition there was also a significant trend toward an association with the combination of the GSTM1 null and GSTT1 null in either East Asians or Mediterraneans. ConclusionThe GSTM1/T1 null polymorphisms may be associated with vitiligo. More studies are needed to confirm this conclusion.

P206 Is prophylactic antibiotics for extracorporeal shock wave lithotripsy necessary? A randomized controlled trial

The frequency of micronuclei (MN) in cultured peripheral lymphocytes was used as a biomarker of genotoxic effects in 34 Italian pesticide-exposed greenhouse workers and 33 unexposed referents matched with the exposed workers for age and smoking habits. The possible influence of the genetic polymorphisms of xenobiotic metabolizing enzymes glutathione S-transferase M1 (GSTM1), T1 (GSTT1), and N-acetyltransferase 2 (NAT2) was also evaluated. To restrict the analysis primarily to cells that have divided once in vitro, MN were scored only in cells showing label after a 42-h incubation with bromodeoxyuridine (BrdU), as detected by immunofluorescence (anti-BrdU technique). Two different concentrations of BrdU (0.5 and 1 μg/ml) were compared. Individual frequencies of micronucleated cells (MNCs) obtained with the two concentrations of BrdU significantly correlated with each other (r=0.55, P<0.001). Higher mean MNCs frequencies (per 1000 cells) were detected among exposed smokers (9.0 at 0.5 μg/ml BrdU and 7.8 at 1 μg/ml BrdU) than in smoking referents (6.3 and 5.9, respectively). In multiple regression analysis controlling for age, sex, smoking and genotypes, a significant elevation of MNC frequency (P=0.004 at 1 μg/ml BrdU; P=0.052 at 0.5 μg/ml BrdU) was observed in greenhouse workers with a work history of extensive pesticide spraying (n=17). Increased MNC frequencies were also associated with ageing at 0.5 μg/ml BrdU, with the GSTM1-positive genotype at both 1 (P=0.028) and 0.5 (P=0.056) μg/ml BrdU in all subjects, and with the NAT2 fast acetylator genotype in smokers at 0.5 μg/ml BrdU (P=0.043). The results indicate that MN rates are increased in greenhouse workers, especially in those involved in pesticide spraying. The GSTM1 positive and NAT2 fast genotypes appear to be associated with elevated MNC frequencies, which contradicts with earlier results on elevated chromosomal aberration rates in GSTM1 null smokers and NAT2 slow subjects.

Atherosclerosis and Vascular Biology

Atherosclerosis and Vascular Biology

GSTM1 and GSTT1 copy numbers and mRNA expression in lung cancer

Large fractions of the human population do not express GSTM1 and GSTT1 (GSTM1/T1) enzymes because of deletions in these genes. These variations affect xenobiotic metabolism and have been evaluated in relation to lung cancer risk, mostly based on null/present gene models. We measured GSTM1/T1 heterozygous deletions, not tested in genome-wide association studies, in 2,120 controls and 2,100 cases from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We evaluated their effect on mRNA expression on lung tissue and peripheral blood samples and their association with lung cancer risk overall and by histology types. We tested the null/present, dominant, and additive models using logistic regression. Cigarette smoking and gender were studied as possible modifiers. Gene expression from blood and lung tissue cells was strongly down regulated in subjects carrying GSTM1/T1 deletions by both trend and dominant models (P < 0.001). In contrast to the null/present model, analyses distinguishing subjects with 0, 1, or 2 GSTM1/T1 deletions revealed several associations. There was a decreased lung cancer risk in never-smokers (OR = 0.44; 95%CI = 0.23-0.82; P = 0.01) and women (OR = 0.50; 95%CI = 0.28-0.90; P = 0.02) carrying 1 or 2 GSTM1 deletions. Analogously, male smokers had an increased risk (OR = 1.13; 95%CI = 1.0-1.28; P = 0.05) and women a decreased risk (OR = 0.78; 95%CI = 0.63-0.97; P = 0.02) for increasing GSTT1 deletions. The corresponding gene smoking and gene-gender interactions were significant (P < 0.05). Our results suggest that decreased activity of GSTM1/T1 enzymes elevates lung cancer risk in male smokers, likely due to impaired carcinogens' detoxification. A protective effect of the same mutations may be operative in never-smokers and women, possibly because of reduced activity of other genotoxic chemicals.

P210 Azathioprine versus azathioprine plus metronidazole for the prevention of postoperative endoscopic recurrence of Crohn's disease: A randomized, placebo-controlled trial

therefore aimed to find genetic and clinical factors predictive of thiopurine induced AE in patients with CD. Methods: Four hundred and sixty eight CD patients were screened and one hundred and eighty one patients treated with thiopurines were included in our study. Thiopurine AE included were myelosuppression, hepatotoxicity and pancreatitis. Clinical data collected included age, ethnicity, gender and smoking status. Patients’ DNAwas tested for specific polymorphisms in the TPMT, GSTM1and GSTT1 genes. Results: Twenty-seven patients (15%) developed AE requiring thiopurine discontinuation. The most common AE was myelosuppression (12 patients), followed by pancreatitis (9 patients) and hepatotoxicity (6 patients). Univariate analysis showed that patients developing AE were significantly older when receiving thiopurines (mean 34.19±14.0 vs. 27.95±11.7 years old, P= 0.016) and more likely to be current or past smokers (51.9% vs 30.0%, P= 0.044). Specifically, patients who developed thiopurine induced pancreatitis were more likely to be past or present smokers (p = 0.001), and patients who developed hepatotoxicity were older than patients who did not develop AE (p = 0.014). Only four patients (2.2%) were heterozygous for TPMT polymorphisms, and none developed thiopurine induced AE. No association was found between GSTM1 or GSTT1 polymorphisms and the development of AE (p = 0.08 for GSTM1 wild-type). On multi-variant analysis past or current smokers were at increased risk for developing thiopurine related AE (OR 2.84, CI 95%: 1.104 7.296). Conclusions: TPMT, GSTM1 and GSTT1 genotype did not predict development of thiopurine induced AE in our patients. Past or current smokers were at increased risk for thiopurine induced AE, specifically pancreatitis. These findings may have implications for decision making in treating CD patients with thiopurines.

Analysis of glutathione S-transferase genes polymorphisms and the risk of schizophrenia in a sample of Iranian population

Glutathione S-transferases (GSTs) are major intracellular antioxidants, which, impaired in their function, are involved in the progress of schizophrenia (SCZ). The aim of this case-control study was to investigate the association between the polymorphism of glutathione S-transferases M1 (GSTM1), T1 (GSTT1), the glutathione S-transferase P1 gene (GSTP1) and SCZ. We isolated genomic DNA from peripheral blood of 93 individuals with SCZ and 99 healthy control subjects' genotypes analyzing them for GSTM1, GSTT1 and GSTP1 using polymerase chain reaction. The analysis of the gene-gene interaction between GSTs indicated that the magnitude of the association was greater for the combined AG/GSTT1 & GSTM1 genotypes (OR=2.51; 95% CI: 1.13-5.63, P=0.02). The AG and combined AG+GG genotypes of GSTP1 increased the risk of SCZ (OR=1.83; 95% CI: 0.94-3.75 and OR=1.71; 95% CI: 0.92-3.19, respectively). The genotypes of GSTT/NULL, NULL/GSTM and NULL/NULL increased the risk of SCZ (OR=2.05; 95% CI: 0.9-4.74; OR=2.0; 95% CI: 1.68-2.31; and OR=1.8; 95% CI: 0.57-2.46, respectively). The present study supports previous data that suggest that impairment in the function of GSTs genes may increase the risk of SCZ.

Glutathione S-transferase M1, T1, and P1 gene polymorphisms and carotid atherosclerosis in Korean patients with rheumatoid arthritis.

We assessed the contribution of genetic polymorphisms of glutathione S-transferase M1 ( GSTM1), T1 ( GSTT1), and P1 ( GSTP1, Ile105Val) to carotid atherosclerosis in 40 postmenopausal rheumatoid arthritic (RA) women without histories of smoking. We measured mean intima-media thickness (IMT) and plaque of the common carotid arteries by ultrasonography and evaluated relationships among the known risk factors for atherosclerosis, genetic polymorphisms, RA outcomes, and markers of inflammation. Subjects with the GSTT1-0 genotype had greater IMT ( P<0.05). On univariate analysis, carotid IMT was positively associated with age, systolic BP, antihypertensive drug use, and the GSTT1-0 genotype ( P<0.05). When compared to subjects with a double-positive GSTM1/T1 genotype, IMT in those with concurrent lack of the GSTM1 and GSTT1 genes was significantly increased ( P=0.008). This study suggests that the GSTT1-0 genotype might have an interaction with carotid atherosclerosis related to RA in Korean postmenopausal RA women without histories of smoking.

Polymorphism of Glutathione S-Transferase Genes M1 and T1 in Patients with Motor Neuron Disease from the Moscow Population

Comparison of the frequency distributions of alleles, genotypes, and genotype combinations of genes GSTM1and GSTT1 did not show statistically significant differences between patients with motor neuron disease (MND) and a random sample from the Moscow population. Apparently, these genes are not involved in MND pathogenesis in these patients.

Increased frequencies of glutathione S-transferase(GSTM1 and GSTT1) gene deletions in Korean patients with acquired aplastic anemia

AbstractPatients with reduced ability to metabolize environmental carcinogens or toxins may be at risk of developing aplastic anemia. Glutathione S-transferase (GST) has been implicated in detoxifying mutagenic electrophilic compounds. This study asked whether the homozygous gene deletions of GSTM1 andGSTT1 affect the likelihood of developing aplastic anemia. The incidence of GSTM1 and GSTT1 gene deletions was significantly higher for aplastic anemia patients (odds ratio [OR]: 3.1, P = .01 and OR: 3.1,P = .004, respectively) than for healthy controls. Among the aplastic anemia patients, 17.5% (10:57) had chromosomal abnormalities at the time of diagnosis, and all aplastic anemia patients with chromosomal abnormalities showedGSTT1 gene deletions (P = .048). Individuals with GSTM1 and GSTT1 gene deletions may have greater susceptibility to aplastic anemia. It is possible that genetic instability or chromosomal damage due to abnormal detoxification of environmental toxins might have worked as an important pathophysiologic mechanism of aplastic anemia for patients with GSTT1 gene deletions.

Modulation of DNA and protein adducts in smokers by genetic polymorphisms in GSTM1,GSTT1, NAT1 and NAT2.

The formation of DNA and protein adducts by environmental pollutants is modulated by host polymorphisms in genes that encode metabolizing enzymes. In our study on 67 smokers, aromatic-DNA adduct levels were examined by nuclease P1 enriched 32P-postlabelling in mononuclear blood cells (MNC) and 4-aminobiphenyl-haemoglobin adducts (4-ABP-Hb) by gas chromatography-mass spectroscopy. Genetic polymorphisms in glutathione S-transferase M1 (GSTM1), T1 (GSTT1) and N-acetyl-transferase 1 (NAT1) and 2 (NAT2) were assessed by polymerase chain reaction-based methods. DNA adduct levels, adjusted for the amount of cigarettes smoked per day, were higher in GSTM1(-/-) individuals (1.30 +/- 0.57 adducts per 108 nucleotides) than in GSTM1(+) subjects (1.03 +/- 0.56, P = 0.05), higher in NAT1 slow acetylators (1.58 +/- 0.54) than in NAT1 fast acetylators (1.11 +/- 0.58, P = 0.05) and were also found to be associated with the NAT2 acetylator status (1.29 +/- 0.64 and 1.03 +/- 0.46, respectively, for slow and fast acetylators, P = 0.06). An effect of GSTT1 was only found in combination with the NAT2 genotype; individuals with the GSTT1(-/-) and NAT2-slow genotype contained higher adduct levels (1.80 +/- 0.68) compared to GSTT1(+)/NAT2 fast individuals (0.96 +/- 0.36). Highest DNA adduct levels were observed in slow acetylators for both NAT1 and NAT2 also lacking the GSTM1 gene (2.03 +/- 0.17), and lowest in GSTM1(+) subjects with the fast acetylator genotype for both NAT1 and NAT2 (0.91 +/- 0.45, P = 0.01). No overall effects of genotypes were observed on 4-ABP-Hb levels. However, in subjects smoking less than 25 cigarettes per day, 4-ABP-Hb levels were higher in NAT2 slow acetylators (0.23 +/- 0.10 ng/g Hb) compared to fast acetylators (0.15 +/- 0.07, P = 0.03). These results provide further evidence for the combined effects of genetic polymorphisms in GSTM1, GSTT1, NAT1 and NAT2 on DNA and protein adduct formation in smoking individuals and indicate that, due to the complex carcinogen exposure, simultaneous assessment of multiple genotypes may identify individuals at higher cancer risk.

Polymorphisms of glutathione-S-transferase genes (GSTP1, GSTM1 andGSTT1) and prostate-cancer risk

Several polymorphic glutathione-S-transferase (GST) enzymes are involved in the metabolism of a number of potential prostate carcinogens and are thought to engage in the transport of steroid hormones. A case-control study was conducted to determine the association of the GSTP1, GSTM1 and GSTT1 polymorphisms and prostate-cancer risk. The study population consisted of 166 patients with previously untreated, histologically proven prostate cancer and 166 age-matched control patients with benign prostatic hyperplasia (BPH), all of them Caucasians. In the GSTP1 gene, 2 polymorphic alleles, GSTP1*B and GSTP1*C, have been described in addition to the wild-type allele, GSTP1*A. Both polymorphic GSTP1 alleles have an A-to-G transition in exon 5, causing an isoleucine-to-valine change. The GSTP1*C allele has an additional transition from C to T. For GSTM1 as well as GSTT1, the polymorphic allele is a deletion of the gene. The proportion of individuals homozygous for the GSTP1 variant alleles (GSTP1*B/*B, GSTP1*B/*C and GSTP1*C/*C) was significantly lower in prostate-cancer patients (4.8%) than in BPH controls (14.5%), and the odds ratio (OR) was 0.24 [95% confidence interval (CI) = 0.09-0.61). The heterozygous genotypes (GSTP1*A/*B and GSTP1*A/*C) were also lower in the cancer group, though this was not significant. On the contrary, no significant effect on prostate-cancer risk was detectable for either GSTM1 (OR = 0.86, 95% CI = 0.55-1.36) or GSTT1 (OR = 0.78, 95% CI = 0.43-1.42). Of the polymorphic GSTs, GSTP1 is the most interesting candidate as a biomarker for prostate-cancer risk as we found a 76% reduced risk in men homozygous for the polymorphic GSTP1 alleles compared to those with wild-type GSTP1.

Micronuclei in blood lymphocytes and genetic polymorphism for GSTM1, GSTT1 and NAT2 in pesticide-exposed greenhouse workers

The frequency of micronuclei (MN) in cultured peripheral lymphocytes was used as a biomarker of genotoxic effects in 34 Italian pesticide-exposed greenhouse workers and 33 unexposed referents matched with the exposed workers for age and smoking habits. The possible influence of the genetic polymorphisms of xenobiotic metabolizing enzymes glutathione S-transferase M1 (GSTM1), T1 (GSTT1), and N-acetyltransferase 2 (NAT2) was also evaluated. To restrict the analysis primarily to cells that have divided once in vitro, MN were scored only in cells showing label after a 42-h incubation with bromodeoxyuridine (BrdU), as detected by immunofluorescence (anti-BrdU technique). Two different concentrations of BrdU (0.5 and 1 μg/ml) were compared. Individual frequencies of micronucleated cells (MNCs) obtained with the two concentrations of BrdU significantly correlated with each other ( r=0.55, P<0.001). Higher mean MNCs frequencies (per 1000 cells) were detected among exposed smokers (9.0 at 0.5 μg/ml BrdU and 7.8 at 1 μg/ml BrdU) than in smoking referents (6.3 and 5.9, respectively). In multiple regression analysis controlling for age, sex, smoking and genotypes, a significant elevation of MNC frequency ( P=0.004 at 1 μg/ml BrdU; P=0.052 at 0.5 μg/ml BrdU) was observed in greenhouse workers with a work history of extensive pesticide spraying ( n=17). Increased MNC frequencies were also associated with ageing at 0.5 μg/ml BrdU, with the GSTM1-positive genotype at both 1 ( P=0.028) and 0.5 ( P=0.056) μg/ml BrdU in all subjects, and with the NAT2 fast acetylator genotype in smokers at 0.5 μg/ml BrdU ( P=0.043). The results indicate that MN rates are increased in greenhouse workers, especially in those involved in pesticide spraying. The GSTM1 positive and NAT2 fast genotypes appear to be associated with elevated MNC frequencies, which contradicts with earlier results on elevated chromosomal aberration rates in GSTM1 null smokers and NAT2 slow subjects.

Glutathione S-transferase M1(GSTM1)、T1(GSTT1)遺伝子多型と発癌感受性について

Glutathione S-transferase M1(GSTM1)、T1(GSTT1)遺伝子多型と発癌感受性について