Joint effect of glutathione S‐transferase genotypes and cigarette smoking on idiopathic male infertility

Inconsistent results of association studies investigated the role of glutathione S–transferase genes in idiopathic male infertility may be explained by ethnical differences in gene–gene and gene–environment interactions. In this study, we investigated a joint contribution of GSTM1, GSTT1 and GSTP1 gene polymorphisms and cigarette smoking to the risk of idiopathic infertility in Russian men. DNA samples from 203 infertile and 227 fertile men were genotyped by a multiplex polymerase chain reaction (GSTM1 and GSTT1 deletions) and PCR‐restriction fragment length polymorphism (GSTP1 I105V) methods. The GSTP1 genotype 105IV was associated with increased risk of male infertility (OR = 1.50 95% CI 1.02–2.20 P = 0.04). Genotype combinations GSTP1 105II/GSTT1 del (G1), GSTM1 del/GSTT1 del (G2) and GSTM1 + /GSTT1 del (G3) were associated with decreased risk of male infertility (P ≤ 0.003), whereas a genotype combination GSTP1 105IV/GSTT1 + (G4) was associated with increased disease risk (P = 0.001). The genotype combinations G3 and G4 showed a significant association with infertility in smokers; however, nonsmokers carriers did show the disease risk. In conclusion, GSTM1, GSTT1 and GSTP1 genes are collectively involved in the development of idiopathic male infertility and their phenotypic effects on the disease risk are potentiated by cigarette smoking.     

Relationship between GSTM1/GSTT1 Null Genotypes and Renal Cell Carcinoma Risk: A Meta-Analysis

The results from the published studies on the relationship between GSTM1/GSTT1 null genotypes and renal cell carcinoma (RCC) risk are still conflicting. This meta-analysis was performed to evaluate the relationship between GSTM1/GSTT1 null genotypes and RCC susceptibility. Association studies were identified from the databases of PubMed, Embase, Cochrane Library, and CBM-disc (China Biological Medicine Database) on 1 February 2012, and eligible investigations from 1950 to 2012 were synthesized using meta-analysis method. Results were expressed as odds ratios (ORs) for dichotomous data, and 95% confidence intervals (CIs) were also calculated. Six studies were identified for the analysis of association between polymorphic deletion of GSTM1/GSTT1 and RCC risk. There was no association between GSTM1/GSTT1 null genotype and RCC susceptibility (GSTM1: N = 6, p-heterogeneity = 0.07, OR = 1.07, 95% CI: 0.85–1.35, p = 0.57; GSTT1: N = 6, p-heterogeneity < 0.00001, OR = 0.98, 95% CI: 0.58–1.65, p = 0.94). Interestingly, null genotype of GSTT1 was associated with RCC risk in Caucasians and Asians (Caucasians: N = 4, p-heterogeneity = 0.38, OR = 0.76, 95% CI: 0.61–0.95, p = 0.01; Asians: N = 1, OR = 2.39, 95% CI: 1.63–3.51, p < 0.00001). For the GSTM1–GSTT1 interaction analysis, the dual null genotype of GSTM1/GSTT1 was not significantly associated with RCC susceptibility (N = 4, p-heterogeneity = 0.006, OR = 1.17, 95% CI: 0.98–1.39, p = 0.09). However, the dual null genotype of GSTM1–GSTT1 was associated with RCC risk in Asians (N = 1, OR = 2.06, 95% CI: 1.36–3.13, p = 0.007). In conclusion, our study results suggest that GSTT1 null genotype is associated with the RCC susceptibility in Caucasians and Asians, and the dual null genotype of GSTM1–GSTT1 is associated with RCC risk in Asians. However, more genetic epidemiological investigations are required to further explore this relationship.     

Glutathione S‐transferase Mu‐1 gene polymorphism in Egyptian patients with idiopathic male infertility

The aim of this study was to examine whether an association exists between glutathione S‐transferase Mu‐1 (GSTM1) gene polymorphism and idiopathic male infertility. Sixty men with primary idiopathic infertility and 60 fertile men, serving as controls, were recruited for the study. The polymorphism was analysed using polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) technique. The frequency of GSTM1 null genotype was observed to be higher in infertile men 40% in comparison with 33.3% in the fertile men, but this difference was not statistically significant. There was statistically significant difference between cases and controls as regards GSTM1 genotype distribution (^MCP = 0.006*) in GSTM1‐positive men. Patients with the GSTM1 null genotype had significantly lower sperm concentrations and total sperm count when compared with patients with GSTM1‐positive genotype. In the control group, men with GSTM1 null genotype had significantly lower sperm concentrations but not total sperm count when compared with men with GSTM1‐positive genotype. The results of this study suggest a possible negative effect of GSTM1 null genotype on the spermatogenic potential of the testis.     

Genetic polymorphisms of glutathione S-transferase M1, T1, and P1, and the assessment of oxidative damage in infertile men with varicoceles from northwestern China

Our objective was to investigate the genetic polymorphisms of the glutathione S-transferase M1, T1, and P1 genes (GSTM1, GSTT1, and GSTP1) and to assess the oxidative damage in infertile men with varicoceles from northwestern China. A total of 65 infertile men with varicoceles and 30 controls were included in the study. Multiplex polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism analyses were used to identify the genotypes. Sperm DNA damage was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL). The levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) were measured by high-performance liquid chromatography with electrochemical detection. The activities of malondialdehyde (MDA) and nitric oxide (NO), and the total antioxidant capacity (TAC) were detected by spectroscopic analysis, and sperm characteristics were measured using computer-assisted semen analysis. The frequencies of the GSTM1, GSTT1, and GSTP1 genotypes were not significantly different between the control and patient groups (P > .05). The percentage of TUNEL-positive sperm and the levels of 8-OH-dG, MDA, and NO were higher but the sperm concentration and motility and the TAC were lower in the patients with the GSTM1, GSTT1, and GSTM1/T1 null genotypes than those in the patients with the GSTM1, GSTT1, and GSTM1/T1 present genotypes (P < .05). However, no significant differences were observed between the GSTP1 A/A and A/G+G/G genotypes (P > .05). Our results suggest that the GSTM1 and GSTT1 null genotypes may predispose sperm to increased oxidative damage in infertile men with varicoceles; however, GSTP1 allelic variation was not significantly different between the patient and control groups in this study.     

Role of glutathione S‐transferase Mu‐1 (GSTM1) polymorphism in oligospermic infertile males

The aim of this study was to examine whether an association exists between glutathione S‐transferase Mu‐1 (GSTM1) gene polymorphism and idiopathic male infertility. Forty‐two men with infertility and 43 fertile men were recruited for this study. GSTM1 gene was analysed using PCR technique. The frequency of GSTM1 null (?) genotype was observed to be 45.2% in infertile men as against 20.09% in fertile men. Subjects with the GSTM1 null genotype had lower sperm concentrations and motility when compared with the subjects with GSTM1‐positive genotype in both the groups. This study shows that the frequency of GSTM1 null (?) genotype is significantly high in infertile males when compared with the frequency in fertile males (OR = 0.32, P = 0.017, 95% CI = 0.124–0.831).     

Association of genetic polymorphism of glutathione S-transferase (GSTM1, GSTT1, GSTP1) with bladder cancer susceptibility

The glutathione-S-transferases (GSTs) comprise a class of enzymes that detoxify carcinogenic compounds by conjugating glutathione to facilitate their removal. Polymorphisms in GSTM1, GSTT1, and GSTP1 genes have been related to risk for bladder cancer. Studies focusing on GSTs gene variants relationship with the risk of bladder cancer have produced conflicting and inconsistent results. We examine the association between genetic polymorphism of glutathione S-transferase P1, GSTM1, GSTT1 genes and development of bladder transitional cell carcinoma (TCC). The study population consisted of 166 histologically confirmed male bladder TCC cases and 332 healthy male controls. Genotyping was done using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method and also investigated combined gene interactions. The GSTP1 Val/Val genotype was significantly associated with bladder cancer (OR = 4.32, 95% CI: 2.64–6.34), whereas the association observed for GSTM1 null (OR = 1.32, 95% CI: 0.82–2.62; P = 0.67) and GSTT1 null genotype (OR = 1.18, 95% CI: 0.79–1.67; P = 0.74) did not reach statistical significance. There was a significant multiple interaction between GSTM1, GSTT1, and GSTP1 genotypes in risk of bladder cancer (P for interaction = 0.02). The risk associated with the concurrent presence of GSTM1 positive and GSTP1 Ile/Val or Val/Val (OR = 3.71, 95% CI: 2.34–5.54) and GSTT1 positive and GSTP1 Ile/Val or Val/Val (OR = 2.66, 95% CI: 1.54–4.72) was statistically significant. Patients carrying GSTP1 Val/Val genotype were at increased risk for developing high-grade (OR = 7.68, 95% CI: 4.73–19.25) and muscle invasive (OR = 10.67, 95% CI: 6.34–21.75) bladder cancer. High risk for bladder TCC also was observed with respect to combined GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 4.76, 95% CI: 2.68–18.72) and GSTM1 null/GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 6.42, 95% CI: 4.76–14.72) genotype variant. This study suggests that the GSTP1 polymorphism and its combination with GSTM1, and GSTT1 may be associated with bladder cancer susceptibility in the Iranian population. Further confirmation in large population-based studies is needed.     

Relationship between GSTM1/GSTT1 Null Genotypes and Renal Cell Carcinoma Risk: A Meta-Analysis

The results from the published studies on the relationship between GSTM1/GSTT1 null genotypes and renal cell carcinoma (RCC) risk are still conflicting. This meta-analysis was performed to evaluate the relationship between GSTM1/GSTT1 null genotypes and RCC susceptibility. Association studies were identified from the databases of PubMed, Embase, Cochrane Library, and CBM-disc (China Biological Medicine Database) on 1 February 2012, and eligible investigations from 1950 to 2012 were synthesized using meta-analysis method. Results were expressed as odds ratios (ORs) for dichotomous data, and 95% confidence intervals (CIs) were also calculated. Six studies were identified for the analysis of association between polymorphic deletion of GSTM1/GSTT1 and RCC risk. There was no association between GSTM1/GSTT1 null genotype and RCC susceptibility (GSTM1: N?=?6, p-heterogeneity?=?0.07, OR?=?1.07, 95% CI: 0.85-1.35, p?=?0.57; GSTT1: N?=?6, p-heterogeneity?相似文献   

Association of GSTT1, GSTM1 and GSTP1 gene polymorphism with aristolochic acid nephropathy

Objective To investigate the association of genetic polymorphisms in glutathione S-transferases T1 (GSTT1), M1 (GSTM1) and P1 (GSTP1) with aristolochic acid nephropathy (AAN) of Chinese people in Wenzhou of China. Methods Fifty-nine patients with AAN (AAN group) including 29 male and 30 female as well as 157 healthy ethnically matched controls (control group) including 93 male and 64 female were enrolled in this study. The genotypes of GSTT1, GSTM1 and GSTP1 were determined by multiple PCR and confronting two-pair primers PCR (CTPP-PCR). Results The genotype frequencies of GSTP1 were in Hardy-Weinberg equilibrium. Compared with the healthy controls, the frequency of GSTT1 null genotype was significantly higher in the patients with AAN (66.1％ vs 48.4％，P<0.05). Risk of AAN for individuals with GSTT1 null genotype was 1.747 fold of those without GSTTI null genotype (95% CI=0.818-3.731). The frequency of GSTM1 null genotype, GSTP1 variant genotypes and GSTP1 G allele in the patients and in the controls were 40.7％, 28.8％, 16.1％ and 47.8％, 31.8％, 17.5％, respectively, which were not significantly different. No significant differences were found in prevalence of GSTM1 and GSTP1 gene distribution between patients and controls. Conclusion GSTT1 gene polymorphism appears to be associated with susceptibility to AAN in Southern China.     

The possible role of NF-κB1 Rs28362491 polymorphism in male fertility of Egyptian population

Male reproductive impairment is responsible for at least 50% of cases of couple infertility. Nuclear factor-kappa B (NF-κB) has been functionally linked to germ cell apoptosis, which may affect human fertility. The aim of this study was to determine the association between the rs28362491 SNP of the NF-κB1 gene and infertility in Egyptian men. In this case–control study, semen and blood samples of 247 infertile men, constituting the case group, and of 113 fertile healthy men as the control group were analysed. All study participants were genotyped for polymorphism of the NF-κB1 gene (rs28362491) by the polymerase chain reaction—restriction fragment length polymorphism (PCR-RFLP) technique. Heterozygous I/D genotype of the NF-κB1 rs28362491 polymorphism was associated with a significantly lower risk of poor semen quality, including asthenozoospermia, astheno–teratozoospermia, and oligo–astheno–teratozoospermia, when compared to I/I genotype (odds ratio = 0.25, 0.26, 0.18, p < .0005, <.0005, <.0005) respectively. Overall, the presence of the D allele was associated with a significantly decreased risk of poor sperm quality as compared to the I allele (odds ratio = 0.56, 0.64, 0.49, p = .050, .038, .001). In conclusion, these results suggest that heterozygosity of the NF-κB1 gene may play a protecting role against male infertility in Egyptians.     

Association of polymorphisms in glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) with idiopathic azoospermia or oligospermia in Sichuan,China

The reported effects of the glutathione S-transferase (GSTs) genes (GSTM1, GSTT1, and GSTP1) on male factor infertility have been inconsistent and even contradictory. Here, we conducted a case-control study to investigate the association between functionally important polymorphisms in GST genes and idiopathic male infertility. The study group consisted of 361 men with idiopathic azoospermia, 118 men with idiopathic oligospermia, and 234 age-matched healthy fertile male controls. Genomic DNA was extracted from the peripheral blood, and analyzed by polymerase chain reaction and restriction fragment length polymorphism analysis. There was a significant association between the GSTP1 variant genotype (Ile/Val + Val/Val) with idiopathic infertility risk (odds ratio [OR]: 1.53; 95% confidence interval [CI]: 1.11–2.11; P = 0.009). Similarly, a higher risk of infertility was noted in individuals carrying a genotype combination of GSTT1-null and GSTP1 (Ile/Val + Val/Val) (OR: 2.17; 95% CI: 1.43–3.31; P = 0.0002). These results suggest an increased risk of the GSTP1 variant genotype (Ile/Val + Val/Val) for developing male factor infertility. Our findings also underrate the significance of the effect of GSTM1 and/or GSTT1 (especially the former) in modulating the risk of male infertility in males from Sichuan, southwest China.     

Lack of association between single polymorphic variants of the mitochondrial nicotinamide adenine dinucleotide dehydrogenase 3, and 4L (MT-ND3 and MT-ND4L) and male infertility

Male infertility is a multifactorial condition associated with different genetic abnormalities in at least 15%–30% of cases. The purpose of this study was to identify suspected correlations between infertility and polymorphisms in mitochondrial NADH dehydrogenase subunits 3 and 4L (MT-ND3 and MT-ND4L) in subfertile male spermatozoa. Sanger sequencing of the mitochondrial DNA target genes was performed on 68 subfertile and 44 fertile males. Eight single nucleotide polymorphisms (SNPs) in MT-ND3 (rs2853826, rs28435660, rs193302927, rs28358278, rs41467651, rs3899188, rs28358277 and rs28673954) and seven SNPs in MT-ND4L (rs28358280, rs28358281, rs28358279, rs2853487, rs2853488, rs193302933 and rs28532881) were detected and genotyped. The genotypes and allele frequencies of the study population have shown a lack of statistically significant association between MT-ND3 and MT-ND4L SNPs and male infertility. However, no statistically significant association was found between the asthenozoospermia, oligozoospermia, teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia and oligoteratozoospermia subgroups of subfertile males. However, rs28358278 genotype of the MT-ND3 gene was reported in the subfertile group but not in the fertile group, which implies a possible role of this SNP in male infertility. In conclusion, the investigated polymorphic variants in the MT-ND3 and MT-ND4L genes did not show any significant association with the occurrence of male infertility. Further studies are required to evaluate these findings. Moreover, the subfertile individuals who exhibit a polymorphism at rs28358278 require further monitoring and evaluation.     

Glutathione S-transferase null genotypes in transitional cell bladder cancer: a case-control study

OBJECTIVES: This study was conducted (1) to examine whether the GSTM1 and GSTT1 null genotypes are risk factors for bladder cancer, and (2) to study a possible association of these genotypes with disease severity. METHODS: This case-control study was undertaken over a 21-month period and included 89 newly diagnosed transitional cell bladder cancer patients and 147 controls; both patients and controls originated from a defined population (residents of the loannina region, Northwestern Greece) and were similar with regard to mean age, male to female ratio and smoking habits. The GSTM1 and GSTT1 genotypes were identified by multiplex polymerase chain reaction on peripheral blood DNA samples. Genotype frequencies among patients and controls were assessed and the association of the genotypes with tumor grade and stage at presentation were statistically evaluated by the chi(2) test. RESULTS: The GSTM1 null genotype was strongly associated with bladder cancer. The odds ratio, attributable and population attributable risks were estimated at 2.76, 0.64 and 0.40, respectively. The correlation between the GSTM1 null genotype with stage, although not statistically significant, was estimated at an odds ratio of 2.6 for invasive disease. The correlation of GSTM1 null genotype with tumor grade did not yield a statistically significant result. The GSTT1 null genotype was not statistically associated with bladder cancer. CONCLUSION: According to our study, individuals with the GSTM1 null genotype carry a substantially higher risk for bladder carcinogenesis. The GSTM1 null genotype is not associated with more aggressive disease in terms of tumor grade, although there is a correlation between this genotype and stage of the disease.     

Increased oxidative damage of sperm and seminal plasma in men with idiopathic infertility is higher in patients with glutathione S-transferase Mu-1 null genotype

Aim： To examine whether a relationship exists between glutathione S-transferase Mu-1 （GSTM1） gene polymorphism and the susceptibility of sperm and seminal plasma from patients with idiopathic infertility to oxidative stress. Methods： Fifty-two men with idiopathic infertility and 60 healthy fertile men were recruited to this study. GSTM1 gene polymorphism was determined by polymerase chain reaction （PCR） and both the infertile and control individuals were divided into GSTM1 null and GSTM1 positive groups according to their GSTM1 gene structure. We compared reactive oxygen species （ROS） generation, malondialdehyde （MDA）, protein carbonyls and glutathione （GSH） concentrations, and glutathione S-transferase （GST） activity in seminal plasma and spermatozoa from infertile patients and controls with respect to GSTM1 genotype. Results： Significantly higher levels of oxidative stress and damage markers were found in idiopathic infertile men with the GSTM1 null genotype compared with those with the GSTM1 positive genotype. There was no significant difference in genotype distribution for theGSTM1 variant between the idiopathic infertile subjects and fertile subjects. Patients with the GSTM1 null genotype also had lower sperm concentrations than those with GSTM1 positive genotype. Conclusion： Our results suggest that the susceptibility of sperm and seminal plasma to oxidative stress is significantly greater in idiopathic infertile men with the GSTM1 null genotype compared with those possessing the gene. Therefore, in patients with idiopathic infertility, GSTM1 polymorphism might be an important source of variation in susceptibility of spermatozoa to oxidative damage.     

谷胱甘肽转硫酶T1、P1和M 1基因多态性与马兜铃酸肾病的关系

2000

2.0.TX;2-R.aspx'>Urotheliai lesion in Chinese-herb nephropathy [其它论文] 1999

Aristolochic acid as a probable human cancer hazard in herbal remedies:a review 2002

Pathologic aspects of a newly described nephropathy related to the prolonged use of Chinese hetbs 1994

Onaran I.Cuven G.Ozaydin A The influence of GSTM1 null genotype on susceptibility to in vitro oxidative stress [其它论文] 2001

Hirvonen A Polymorphisms of xenobiotic-metabolizing enzymes and susceptibility to cancer [其它论文] 1999(zl)

Pemble S.Schroeder KR.Spencer SR Human glutathione S-transferase theta (GSTTl):cDNA cloning and the characterization of a genetic polymorphism 1994

Harries LW.Stubbins MJ.Forman D Identification of genetic polymorphisms at the glutathione S-transferases Pi locus and association with susceptibility to bladder,testicular and prostate cancer [其它论文] 1997

苏涛.屈磊.张春丽 马兜铃酸Ⅰ在大鼠体内的代谢特征研究 [其它论文] -中国中药杂志2004

Jeronimo C.Varzim G.Henrique R I105V polymorphism and promoter methylatinn of the GSTP1 gene in prostate adenocarcinoma 2002

Sweeney C.Farrow DC.Schwartz SM Glutathinne Stransferase M1,T1,and P1 polymorphisms as risk factors for renal cell carcinoma:a case-control study 2000

Zhong S.Wyllie AH.Barnes D Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder,breast and colon cancer 1993

Garte S.Gasped L.Alexandrie AK Metabolic gene polymorphism frequencies in control populations [其它论文] 2001

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Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) and prostate cancer: a case-control study in Tehran, Iran

We evaluated the relationship between polymorphisms in the glutathione S-transferases (GSTs) GSTM1, GSTT1 and GSTP1 genes and prostate cancer (PCa). PCR-restriction fragment length polymorphism assay was used to genotype the GSTM1, GSTT1, and GSTP1 polymorphisms in 168 PCa cases and 336 frequency matched controls. The GSTM1 null, and GSTT1 null genotypes were associated with an increased odds ratio (OR) for PCa (OR=3.28, 95% confidence interval (CI): 2.47-5.64; P=0.005, and OR=3.21, 95% CI: 2.52-5.64; P=0.005, respectively) (Pcorrected=0.0062). The frequency of GSTP1 Val/Val genotype was 14.3% in cases compared with 2.4% in controls, this polymorphism thus being associated with a significantly increased risk of PCa (OR=3.72, 95% CI: 1.67-5.65; P=0.002). The risk associated with the concurrent absence of both of the genes (OR=4.8, 95% CI: 2.34-6.78) was greater than the product of risk in men with either null (OR=1.52, 95% CI: 0.82-2.31) genotype combinations (P=0.001, Pcorrected=0.0045). The combination of GSTP1 Ile/Val or Val/Val polymorphism with the GSTT1 null and GSTM1 null type resulted in an OR of 6.21 (95% CI: 4.83-16.87) (P=0.0001, Pcorrected=0.0062). A higher frequency of the GSTM1 null genotype and GSTT1 null genotype was observed in patients with Gleason score >7, with an OR for GSTM1 null 4.67 (95% CI: 3.64-7.62; P=0.001) and with an OR for GSTT1 null 3.62 (95% CI: 2.31-5.74; P=0.004). The results obtained demonstrated that simultaneous presence of three potentially risk alleles (GSTM1 null, GSTT1 null and GSTP1 Val) lead to a significant OR increase for PCa.     

Influence of genetic polymorphisms in GSTM1, GSTM3, GSTT1 and GSTP1 on allograft outcome in renal transplant recipients

Abstract: Introduction: Glutathione S‐transferases (GSTs) are important in protection against xenobiotic compounds and toxicity caused by immunosuppressants in renal transplant recipients. In the present study we hypothesize that genetic variability in GSTM1, GSTM3, GSTP1 and GSTT1 genes may be associated with allograft outcome. Methods: The study included 223 controls and 273 transplant recipients categorized into 184 stable graft function (SGF), 57 rejection episodes (RE) and 32 delayed graft function (DGF). The polymorphism was studied using multiplex PCR and PCR‐RFLP. Results: GSTM1 null genotype showed a 3.35‐fold higher risk for rejection in SGF vs. RE category [95% confidence interval (CI) 1.27–8.84, p = 0.014]. Mutant (G) allele of GSTP1 was associated with a 5.52‐fold risk for DGF (95% CI 1.37–22.17, p = 0.016). Kaplan–Meier analysis revealed significantly lower mean time to first RE in null genotype as compared with GSTM1 present patients (Log p = 0.002). The dose adjusted C₂ levels in null genotype was higher as compared with GSTM1 present patients at one (p = 0.007) and three months (p = 0.027) post transplantation. Conclusion: Patients with variant genotype of GSTM1 and GSTP1 were at higher risk for rejection and delayed functioning of the allograft, respectively, supporting the hypothesis for involvement of GST isoform variants in allograft outcome in renal transplant recipients.     

An updating meta‐analysis of the GSTM1, GSTT1, and GSTP1 polymorphisms and prostate cancer: A HuGE Review

It has been postulated that individuals with GSTM1, GSTT1 deficiency and, GSTP1 (105Ile/Val transition) have increased susceptibility to carcinogens and are more likely to develop prostate cancer. In recent years, GST status has been extensively studied as a prostate cancer risk factor; however, the results are inconsistent. To re‐examine this controversy, we have undertaken an updating meta‐analysis of 29 studies with GSTM1 genotyping (4,564 prostate cancer cases and 5,464 controls), 22 studies with GSTT1 genotyping (3,837 cases and 4,552 controls), and 24 studies with GSTP1 genotyping (5,301 cases and 5,621 controls). The random effects odds ratio was 1.33 [95% confidence interval (95% CI): 1.15, 1.55; I² = 68.9%, P for heterogeneity = 0.00] for the GSTM1 null versus present genotype and 1.05 (95% CI: 0.86, 1.27; I² = 68.2%, P for heterogeneity = 0.00) for the GSTT1 null versus present genotype, and 1.06 (95% CI: 0.91, 1.24; I² = 71.5%, P for heterogeneity = 0.00) for the GSTP1‐Val versus GSTP1‐Ile allele. For GSTM1 polymorphism, similar results reached in Caucasians and Asians, with exception for Africans. No association between GSTT1 or GSTP1 polymorphisms and prostate cancer risk was detected in different racial. In conclusion, the major finding of our study suggested that GSTM1 polymorphism conferred an increasing risk of prostate cancer on a wide population basis, however, no relationship was found between GSTT1 and GSTP1 status and the risk of prostate cancer. Prostate 69:662–688, 2009. © 2009 Wiley‐Liss, Inc.     

Relationship between GSTs Gene Polymorphism and Susceptibility to End Stage Renal Disease among North Indians

Background and Objective. Glutathione-S-transferase (GST) is the superfamily of genes that provides protection to the cells against reactive oxygen species and plays a vital role in phase II of biotransformation of many substances. Overexpression of GST (EC 2.5.1.18) has been documented in the erythrocytes of patients with chronic renal failure, which may be of clinical relevance. Keeping this background in mind, we have investigated the relationship between human GST gene polymorphism in end stage renal disease (ESRD) patients. Design and Methods. We have assessed 184 patients with ESRD and 569 age-and sex-matched controls from North India. The GSTT1 and GSTM1 null genotypes were identified by polymerase chain reaction (PCR). GSTP1–313 A/G mutation was determined by PCR followed by restriction enzyme digestion. Results. The gene frequency of GSTM1, GSTT1, and GSTP1 polymorphism were evaluated. We observed that GSTM1 null genotype was present in 46.74% of the ESRD patients while GSTT1 null genotype was present in 58.7% of the ESRD subjects. The genotypic distribution of GSTP1 was Ile₁₀₅/Ile₁₀₅ in 47.3%, Ile₁₀₅/Val₁₀₅ in 30.97% and Val₁₀₅/Val₁₀₅ in 21.74% of ESRD patients. There was a significant association of null alleles of the GSTM1 (p = 0.0386; OR = 1.445, 95% CI = 1.033–2.021) and GSTT1 (p ≤ 0.0001; OR = 4.568, 95% CI = 3.215–6.492) and in the -313 G alleles (Val) of the GSTP1 gene (p = 0.0032; OR = 1.956, 95% CI = 1.265–3.024) with end stage renal disease. The combined analysis of the three genotypes showed a further increased risk to ESRD (p ≤ 0.0001; OR = 9.01, 95% CI = 5.55–14.626). Interpretations and Conclusions. The null / low polymorphism of the detoxifying enzymes GSTT1, GSTM1, and GSTP1 are associated with the risk of developing ESRD in North Indian patients.     

Do glutathione-S-transferase polymorphisms influence response to intravenous cyclophosphamide therapy in idiopathic nephrotic syndrome?

The response to cyclophosphamide (CP) is variable and difficult to predict in children with idiopathic nephrotic syndrome (INS). The polymorphic expression of glutathione-S-transferase (GST) may affect the remission rate after CP therapy. In this study, we evaluated the correlation of GST polymorphism and response to CP in INS. We studied GST polymorphism in 74 children with steroid-sensitive (44) and steroid-resistant (30) INS receiving intravenous cyclophosphamide (IVCP) therapy. We correlated GSTM1, GSTT1, and GSTP1 genotypes with response to IVCP. Thirty-seven (50%) out of 74 children responded to CP therapy. A synergistic effect of three genotypic combinations showed significant correlation with remission in the steroid-sensitive group. These combinations were GSTP1 and GSTM1 null genotype (p = 0.013) and GSTP1 together with GSTM1 and GSTT1 null genotypes (p = 0.026). Further, a significant difference was observed with a combination of GSTM1 and GSTT1 null genotypes and Val105 polymorphism. No association was observed among steroid-resistant patients. Our results indicate that among children with steroid-sensitive NS, there is an association with response to IVCP therapy and combination of GSTP1 Val105 polymorphism and the null genotypes of GSTT1 and GSTM1. GST polymorphism may be of significance in the management of children with INS receiving CP therapy.     

甲母痣恶变易感性与谷胱苷肽S转移酶M1、谷胱苷肽S转移酶T1基因缺失的关系

目的 探讨谷胱苷肽S转移酶M1(GSTM1)、谷胱苷肽S转移酶T1(GSTT1)基因缺失与甲母痣恶变之间的关系.方法 采用聚合酶链反应(PCR)技术检测77例甲母痣恶变患者和107例甲母痣患者中GSTM1、GSTT1基因缺失的频率.结果 病例组GSTM1基因缺失的频率为58.4%,显著高于对照组的缺失频率42.1%(x2=4.811,P＜0.05),危险度分析得出OR=1.938,95%CI为1.070～3.509;病例组GSTT1基因缺失的频率为57.1%,接近对照组50.5%的水平(x2=0.802,P＞0.05).联合分析表明两基因在甲母痣恶变发生中具有协同作用.结论 GSTM1基因缺失或GSTM1、GSTT1基因联合缺失在甲母痣恶变患者中发生频率增高,能增加甲母痣恶变的易感性.