Increased prevalence of GSTM(1) null genotype in patients with myelodysplastic syndrome: a case-control study

BACKGROUND AND OBJECTIVE: Myelodysplastic syndromes (MDS) are clonal disorders of bone marrow stem cells characterized by ineffective hematopoiesis leading to blood cytopenia; they often progress to acute myeloid leukemia (AML). The glutathione S-transferases (GST) detoxify various agents, including those implicated in MDS. Both GSTM(1) and GSTT(1) genes have "null" alleles and are polymorphic. We studied the impact of GTM(1) and GSTT(1) null genotypes on the MDS susceptibility, disease severity and laboratory indices with prognostic value for the syndrome. MATERIAL AND METHODS: In a hospital-based case-control study we analyzed lymphocyte DNA samples from 54 patients with MDS and 60 cancer-free controls matched for age, sex, smoking habits and origin. A multiplex polymerase chain reaction was used to genotype both GSTM(1) and GSTT(1) simultaneously. The chi(2) test was used for statistical evaluation of the data and the odds ratios and attributable risk and population attributable risk were also calculated. RESULTS: A significantly increased frequency of GSTM(1) null genotype was found among MDS patients (57.4%) compared to controls (33.3%) (p < 0.01), while the frequency of GSTT(1) null genotype was not significantly higher in MDS patients (11.1% vs. 6.66%). Neither GSTM(1) and GSTT(1) null genotype was associated with a particular category of the French-American-British (FAB) classification in the patients studied. Additionally, GSTM(1) null genotype was associated with a significant decrease in the absolute number of neutrophils among the MDS patients. CONCLUSIONS: Individuals with GSTM(1) null genotype may have increased susceptibility to MDS. Null genotypes do not seem to have be associated with FAB classification while they may be associated with putative prognostic factors.     

GSTT1及GSTM1与急性髓系白血病疗效及预后的研究

目的探讨谷胱甘肽硫转移酶(GSTs)家族中GSTT1和GSTM1基因多态性与急性髓系白血病(AML)疗效,药物不良反应与预后的关系。方法AML患者180例,用多重PCR方法检测GSTT1和GSTM1基因型,比较不同基因型患者的诱导治疗完全缓解(CR)率,药物不良反应发生率,总体生存期,无复发生存期和复发率。结果(1)GSTT1和GSTM1基因双非缺失型(double-present型)患者一疗程CR率高于GSTT1,GSTM1任一基因缺失型(null型),二者差异有统计学意义(P=0.013),GSTT1/GSTM1的null基因型患者发生不CR的危险度是double-present型患者的8.736倍(95%CI1.146~66.574)。GSTT1present型一疗程CR率高于GSTT1null型,二者比较亦有统计学意义(P=0.021,OR=2.572,95%CI1.136~5.826);(2)GSTT1和GSTM1基因型分布与诱导治疗后中性粒细胞<0.5×109/L及PLT<20×109/L持续时间差异无统计学意义,GSTM1null型患者发生AST异常的危险度是GSTM1present型的2.593倍(P=0.016,95%CI1.176~5.717);(3)double-present型总体和无复发生存期较GSTT1/GSTM1的null型患者长(平均总体生存期为68.4、38.5个月,P=0.028;平均无复发生存期为73.5、34.9个月,P=0.014),GSTT1null型患者无复发生存期短于GSTT1present型患者(平均无复发生存期为26.7、64.3个月,P=0.038),但二者总体生存期无统计学意义(P=0.653)。double-present型患者复发率显著低于GSTT1/GSTM1的null型患者(13.3%、35.6%,P=0.019)。结论GSTT1,GSTM1基因型与AML患者治疗CR率、复发率、化疗的不良反应及预后均有显著相关性,GSTT1和GSTM1基因型有助于指导AML患者个体化治疗方案的制定。     

Polymorphisms of the glutathione S-transferases mu-1 (GSTM1) and theta-1 (GSTT1) and the risk of advanced alcoholic liver disease

OBJECTIVE: The aim of this study was to determine whether null genotypes for glutathione transferase mu-1 (GSTM1) and theta-1 (GSTT1) influence the risk of development of advanced alcoholic liver disease. MATERIAL AND METHODS: GSTM1 and GSTT1 genotypes were identified on DNA through multiple analysis with polymerase chain reaction in 153 subjects diagnosed with advanced alcoholic liver disease and in 241 healthy controls. RESULTS: The frequency of the GSTM1 null genotype was not different between patients and controls (36.6% versus 41.1%, non-significant). The GSTT1 null genotype was more frequently found in patients than in controls (32% versus 22%, odds ratio 1.67, 95% CI 1.03-2.71, p =0.027). Moreover, patients were more likely to be simultaneous carriers of both GSTM1 and GSTT1 null genotypes (odds ratio 4.30, 95% CI 1.89-9.97, p =0.0003). CONCLUSIONS: The GSTT1 null genotype is more frequent among patients with advanced alcoholic liver disease than in controls. The coincidence of this genotype with the GSTM1 null genotype is four times more likely in patients. We suggest that polymorphisms affecting the activity of the glutathione S-transferase isoforms M1 and T1 may be associated with the risk of developing chronic severe ethanol liver damage.     

Glutathione-S-transferase （GSTM1, GSTrl） and the risk of gastrointestinal cancer in a Korean population

AIM: To evaluate the association of glutathione S-transferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) null genotypes with the risk of gastric cancer (GC) and colorectal cancer (CRC) in a South Korean population.METHODS: We conducted a population-based, large-scale case-control study including 2213 GCs, 1829 CRCs, and 1699 controls. Null and non-null genotypes of GSTM1 and GSTT1 were determined using real-time PCR.RESULTS: The null genotypes of GSTM1 and GSTT1 were not significantly associated with elevated risk of gastric (OR = 1.070, 95% CI = 0.935-1.224; OR = 1.101, 95% CI = 0.963-1.259, respectively) or colorectal cancer (OR = 1.065, 95% CI = 0.923-1.228; OR = 1.041, 95% CI = 0.903-1.200, respectively). The frequency of the combined null GST genotype was not different between the two cancer groups and controls. Moreover, smoking, drinking, and age did not modify the association between these genotypes and the risk of gastric or colorectal cancer.CONCLUSION: GSTM1 and GSTT1 null genotypes were not associated with increased risk of GC or CRC in Koreans.     

Glutathione-S-transferase (GSTM1, GSTT1) and the risk of gastrointestinal cancer in a Korean population

AIM: To evaluate the association of glutathione S-transferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) null genotypes with the risk of gastric cancer (GC) and colorectal cancer (CRC) in a South Korean population.METHODS: We conducted a population-based, largescale case-control study including 2213 GCs, 1829CRCs, and 1699 controls. Null and non-null genotypes of GSTM1 and GSTT1 were determined using realtime PCR.RESULTS: The null genotypes of GSTM1 and GSTT1 were not significantly associated with elevated risk of gastric (OR = 1.070, 95% CI = 0.935-1.224; OR = 1.101, 95% CI = 0.963-1.259, respectively) or colorectal cancer (OR = 1.065, 95% CI = 0.923-1.228; OR = 1.041, 95% CI = 0.903-1.200, respectively). The frequency of the combined null GST genotype was not different between the two cancer groups and controls.Moreover, smoking, drinking, and age did not modify the association between these genotypes and the risk of gastric or colorectal cancer.CONCLUSION: GSTM1 and GSTT1 null genotypes were not associated with increased risk of GC or CRC in Koreans.     

Polymorphisms within glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a case-control study

Glutathione S-transferases (GSTs) have been associated with outcome in human cancers treated with cytotoxic chemotherapy. In a case-control study, we investigated the association between polymorphisms within the GSTM1, GSTT1, and GSTP1 genes and risk of relapse in childhood acute lymphoblastic leukemia (ALL). Cases were relapsed patients. Controls were successfully treated patients with a minimum follow-up of 5 years. The null genotype (absence of both alleles) for GSTM1 or GSTT1 conferred a 2-fold (OR = 0.5, 95% CI = 0. 23-1.07, P =.078) and 2.8-fold (OR = 0.36, 95% CI = 0.13-0.99, P =. 048) reduction in risk of relapse, respectively, relative to the presence of the GSTM1 or GSTT1 gene. The GSTP1 Val(105)/Val(105) genotype showed a 3-fold decrease in risk of relapse (OR = 0.33, 95% CI = 0.09-1.23, P =.099) in comparison to the combined category of Ile(105)/Val(105) and Ile(105)/Ile(105 )genotypes. No particular associations with relapse were observed for the GSTP1 polymorphism at codon 114. The risk of relapse when having 1 of the low-risk genotypes (GSTM1 null, GSTT1 null, GSTP1 Val(105)/Val(105)) decreased 1.9-fold (OR = 0.53, 95% CI = 0.24-1.19, P =.123), and the risk when having 2 or 3 low-risk genotypes 3.5-fold (OR = 0.29, 95% CI = 0.06-1.37, P =.118), compared with individuals having no low-risk genotype (P for trend =.005). Our results suggest that polymorphisms within genes of the GST superfamily may be associated with risk of relapse in childhood ALL. (Blood. 2000;95:1222-1228)     

Glutathione-S-transferase gene polymorphisms (GSTT1, GSTM1, GSTP1) as increased risk factors for asthma

OBJECTIVES: Asthma is a complex multifactorial disease with an obvious genetic predisposition, immunological aberration, and involvement of noxious environmental factors. Polymorphisms of the glutathione-S-transferase (GST) genes are known risk factors for some environmentally-related diseases. In the present study, the hypothesis that polymorphisms in the GSTT1, GSTM1 and GSTP1 genes are associated with atopic and nonatopic asthma was examined. METHODOLOGY: The study population consisted of 103 unrelated healthy individuals and 101 patients with bronchial asthma (64 atopic, 37 nonatopic). Asthma was diagnosed according to the American Thoracic Society statement. Genotyping of polymorphisms in the GSTT1, GSTM1 and GSTP1 genes was performed using real time polymerase chain reaction with a Light Cycler instrument and hybridization probes in combination with the Light Cycler DNA master hybridization probes kit. RESULTS: Patients with atopic asthma (34.4%) had a higher prevalence of the GSTT1 null genotype than the nonatopic asthma patients (13.5%; OR = 3.83; 95% CI, 1.24-11.78). Asthma patients (63.4%) had a higher prevalence of the GSTM1 null genotype than the control group (40.8%; OR = 2.34; 95% CI, 1.31-4.20). Subjects with the GSTP1 homozygous Val/Val genotype had a 3.55-fold increased risk of having atopic asthma compared to nonatopic asthma (OR = 3.55; 95% CI, 1.10-12.56). CONCLUSIONS: These results suggest that the GSTT1 and GSTM1 null genotypes and the GSTP1 Val/Val polymorphism may play important roles in asthma pathogenesis. It is possible that intermediate electrophilic metabolites, arising in the first phase of detoxification, are not metabolized by GST enzymes in asthmatic patients and are not excreted. These intermediate metabolites may damage cells and generate oxidative stress, and so contribute to the pathogenesis of asthma.     

谷胱甘肽S-转移酶M1、T1基因多态与散发性大肠腺癌遗传易感性

目的　探讨谷胱甘肽S 转移酶 (GST)M1、T1基因多态与散发性大肠腺癌 (SCRAC)遗传易感性的关联。方法　应用多重聚合酶链反应 (PCR)技术 ,对经病理组织学确诊的 10 4例SCRAC患者及同期在本院体检的无血缘关系的 10 1例健康人 ,检测其GSTM1和GSTT1基因多态性。结果　 (1)在健康人和SCRAC患者 ,GSTM1、GSTT1空白基因型的频率差异均无显著性 (前者 4 6 5 % :5 6 7% ,χ2 =2 13,P >0 0 5 ;后者 4 7 5 % :6 0 6 % ,χ2 =3 5 2 ,P >0 0 5 )。 (2 )GSTM1空白基因型频率在近端与远端SCRAC患者间、在老年与非老年SCRAC间的频率差异均无显著性 ;而GSTT1空白基因型的频率差异有显著性 (前者 4 4 4 % :6 6 2 % ,χ2 =3 97,P <0 0 5 ;后者 70 9% :4 9 0 % ,χ2 =5 2 1,P <0 0 5 )。 (3)GSTM1、GSTT1均为空白基因联合型的个体患SCRAC的危险性升高 4 33倍 (9 6 % :2 6 9% ,χ2 =7 89,ν =3,P <0 0 5 )。结论　单独的GSTM1或GSTT1空白基因型与SCRAC遗传易感性无关 ,但GSTT1空白基因型与远端SCRAC遗传易感性有关 ,且多见于老年患者。GSTM1、GSTT1均为空白基因的联合基因型是SCRAC的易感基因型。     

Possible Influence of Glutathione <Emphasis Type="Italic">S</Emphasis>-Transferase <Emphasis Type="Italic">GSTT1</Emphasis> Null Genotype on Age of Onset of Sporadic Colorectal Adenocarcinoma

INTRODUCTION: Glutathione S-transferase enzymes mediate exposure to cytotoxic and genotoxic agents and may be involved in cancer susceptibility. Both glutathione S-transferase mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. The association of glutathione S-transferase null genotype and risk of developing colorectal cancer is not yet fully clarified. METHODS: We tested whether the null genotypes for GSTM1 and GSTT1 genes altered the risk for sporadic colorectal adenocarcinoma in Brazilian patients. Genomic DNA from 102 sporadic colorectal adenocarcinoma patients and 300 controls was analyzed by polymerase chain reaction. RESULTS: Frequencies of GSTM1, GSTT1, and null combined genotypes were similar in patients and controls (49.9 vs. 44.6 percent, 16.6 vs. 17.3 percent, and 8.8 vs. 8 percent, respectively). We found a 1.03-fold (95 percent confidence interval, 0.96-1.10) and 1.08-fold (95 percent confidence interval, 0.99-1.18) increased risk associated with GSTM1 and GSTT1 null genotypes, respectively (P = 0.45 and P = 0.08) and a 1.18-fold (95 percent confidence interval, 0.47-2.90) increased risk associated with the combined null genotype (P = 0.74). The GSTT1 null genotype was more common in patients who were diagnosed before the age of 60 years than in those who were diagnosed at an older age (28.8 vs. 4 percent, respectively; P = 0.0008). CONCLUSIONS: The results suggest that inherited absence of this carcinogen detoxification pathway may not be associated with sporadic colorectal adenocarcinoma in the present cases. However, a higher frequency of GSTT1 null genotype in patients diagnosed before the age of 60 years suggests that this genotype could influence the age of disease onset in Brazil.     

Combined GSTM1 and GSTT1 null genotypes are associated with a lower risk of papillary thyroid cancer

Individual susceptibility to cancer is influenced by polymorphisms of genes encoding drug-metabolizing enzymes such as the glutathione S-transferases (GST). The null polymorphisms of the GSTM1 and GSTT1 genes have been associated to a modified risk of several cancers but studies of thyroid cancer have produced conflicting results. The aim of this study was to investigate the relationship between these polymorphisms and the risk of papillary thyroid cancer (PTC). A total of 188 patients with PTC and 247 controls were genotyped using a PCR-based assay. Odds ratios (OR) and 95% confidence intervals (CI) for each homozygous null genotype were determined. The frequency of each of the GSTM1 and GSTT1 null genotypes did not differ significantly between patients and controls (OR=0.83, 95%CI: 0.56-1.21; p=0.328; and OR=0.66, 95%CI: 0.39-1.12; p=0.123, respectively), but the frequency of individuals that had the combined GSTM1 null/GSTT1 null genotypes was significantly lower in the patient group (OR=0.50, 95%CI: 0.26-0.97; p=0.040). The GSTM1 null genotype was associated with a lower risk of advanced cancer stages (III/IV) (OR=0.50, 95%CI: 0.26-0.96; p=0.036) and the GSTT1 null genotype was associated with a lower risk of the follicular variant of PTC (OR=0.31, 95%CI: 0.10-0.97; p=0.044). These results suggest that GSTM1 and GSTT1 null genotypes are weak, yet possible, modifiers of the risk of PTC. This protective effect may be due to a role of the GSTM1 and GSTT1 encoded enzymes in the metabolic activation of putative thyroid carcinogens or in other pathways involved in thyroid carcinogenesis.     

Polymorphisms at GSTM1 and GSTT1 gene loci and susceptibility to cervical cancer in Indian population

Multiple allelism at loci encoding detoxifying enzymes is associated with cancer risk. Glutathione S-transferase (GSTs) catalyzes the conjugation of glutathione to numerous potentially genotoxic compounds. This study evaluates the influence of genetic polymorphisms of GST M1 and GST T1 on susceptibility to cervical cancer. A multiplex polymerase chain reaction method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in genomic DNA isolated from cases with cervical cancer (n=142) and normal controls (n=96). The results showed that the frequency of homozygous GSTM1 null genotype was higher in cervical cancer cases (57.0%) as compared to controls (34.4%) and the differences were significant (p<0.05), OR=2.5, 95% CI: 1.4--4.5. The frequency of homozygous GSTT1 null genotype in cancer cases was 19.7% in comparison to 12.5% in controls, however, the difference was not statistically significant (OR=1.7, 95% CI: 0.8-3.8). Significant difference was found between the cases and controls in the distribution of the null genotype of GST M1 in individuals aged above 45 years (p=0.04), but this difference was not significant in individuals aged below 45 years (p=0.06). No significant differences were found in cervical cancer cases and controls when data were analyzed according to age group for GSTT1 null genotype. Further, the combined analysis of both GSTM1 null and GSTT1 null genotypes did not appear to influence the susceptibility to cervical cancer, suggesting that polymorphisms of other detoxifying enzymes may play a significant role in cervical carcinogenesis.     

谷胱甘肽硫转移酶M1和T1基因多态性与燃煤型砷中毒发病的关系

目的探讨谷胱甘肽硫转移酶M1和T1（GSTM1、GSTT1）基因多态性与燃煤污染型砷中毒发病风险的关系。方法采用多重等位基因特异聚合酶链反应技术检测贵州省130名燃煤型砷中毒患者及140名健康个体的GSTM1和GSTT1基因多态性，并分析不同基因型与砷中毒发病的关系。结果砷中毒病例组和对照组GSTT1纯合缺失基因型（GSTT1^（-/-））的频率分别为58．5％和45．0％，组间比较差异有统计学意义（Х^2=6．246，P〈0．05）；携带GSTT1^（-/-）基因型个体发生砷中毒的风险是携带GSTT1非纯合缺失基因型（GSTT1^（＋/＋）or（-/-））个体的2．18倍[比值比（OR）adj=2．18，95％可信区间（CI）：1．183～4．018]。砷中毒病例组和对照组间GSTM1纯合缺失基因型（GSTM1^（-/-））频率的差异无统计学意义（P〉0．05）。基因型联合分析显示：携带GSTM1^（-/-）和GSTT1^（-/-）联合基因型的个体，其砷中毒的发病风险显著增加（ORadj=2．931，95％CI：1．024～8．387）。结论GSTT1^（-/-）基因型可能是燃煤型砷中毒发生的重要危险内因之一。     

Glutathione S-transferase M null homozygosity and risk of systemic lupus erythematosus associated with sun exposure: a possible gene-environment interaction for autoimmunity

OBJECTIVE: Multiple genetic factors modulate predisposition to systemic lupus erythematosus (SLE). The glutathione S-transferase (GST) genes GSTM1, GSTT1, and GSTP1 catalyze metabolic pathways for the excretion of reactive oxygen species that may be generated by cellular oxidative stress induced by ultraviolet radiation in sunlight. We hypothesized that risk of SLE associated with occupational sun exposure is modulated by GSTM1, GSTT1, and GSTP1 genotypes. METHODS: DNA samples and occupational history were collected from 243 cases and 298 controls in the Carolina Lupus Study, a population based case-control study of patients with recently diagnosed SLE. RESULTS: There was no independent association between SLE and presence of the homozygous null GSTM1 or GSTT1 genotype, the homozygous Val/Val or heterozygous Val/Ile GSTP1 genotype, or occupational sunlight exposure. The prevalence of Ro autoantibodies was significantly increased among Caucasians with the GSTM1 null genotype (OR 2.6, 95% CI 1.0, 6.8), but was somewhat weaker among African-Americans (OR 1.5, 95% CI 0.7, 3.5). In the combined analysis of occupational sunlight exposure and GSTM1 genotype, the effect of sun exposure among Caucasians varied depending on GSTM1 genotype. There was a 3-fold increased risk (OR 3.1, 95% CI 0.9, 10.8) of SLE associated with 24 or more months' occupational sun exposure among Caucasians with the GSTM1 null genotype, but sun exposure was not associated with risk among GSTM1 positive Caucasians (OR 0.6, 95% CI 0.3, 1.5). The interaction was statistically significant (p = 0.028). CONCLUSION: Our results suggest that GSTM1 homozygous null genotype may modify the effect of occupational sun exposure on the risk of SLE in caucasians.     

Polymorphisms of the glutathione S-transferases mu-1 (GSTM1) and theta-1 (GSTT1) and the risk of advanced alcoholic liver disease

Objective. The aim of this study was to determine whether null genotypes for glutathione transferase mu-1 (GSTM1) and theta-1 (GSTT1) influence the risk of development of advanced alcoholic liver disease. Material and methods. GSTM1 and GSTT1 genotypes were identified on DNA through multiple analysis with polymerase chain reaction in 153 subjects diagnosed with advanced alcoholic liver disease and in 241 healthy controls. Results. The frequency of the GSTM1 null genotype was not different between patients and controls (36.6% versus 41.1%, non-significant). The GSTT1 null genotype was more frequently found in patients than in controls (32% versus 22%, odds ratio 1.67, 95% CI 1.03–2.71, p=0.027). Moreover, patients were more likely to be simultaneous carriers of both GSTM1 and GSTT1 null genotypes (odds ratio 4.30, 95% CI 1.89–9.97, p=0.0003). Conclusions. The GSTT1 null genotype is more frequent among patients with advanced alcoholic liver disease than in controls. The coincidence of this genotype with the GSTM1 null genotype is four times more likely in patients. We suggest that polymorphisms affecting the activity of the glutathione S-transferase isoforms M1 and T1 may be associated with the risk of developing chronic severe ethanol liver damage.     

Negative prognostic value of glutathione S-transferase (GSTM1 and GSTT1) deletions in adult acute myeloid leukemia

Glutathione S-transferases (GSTs) are enzymes involved in the detoxification of several environmental mutagens, carcinogens, and anticancer drugs. GST polymorphisms resulting in decreased enzymatic activity have been associated with several types of solid tumors. We determined the prognostic significance of the deletion of 2 GST subfamilies genes, M1 and T1, in patients with acute myeloid leukemia (AML). Using polymerase chain reactions, we analyzed the GSTM1 and GSTT1 genotype in 106 patients with AML (median age, 60.5 years; range, 19-76 years). The relevance of GSTM1 and GSTT1 homozygous deletions was studied with respect to patient characteristics, response to therapy, and survival. Homozygous deletions resulting in null genotypes at the GSTM1 and GSTT1 loci were detected in 45 (42%) and 30 (28%) patients, respectively. The double-null genotype was present in 19 patients (18%). GST deletions predicted poor response to chemotherapy (P =.04) and shorter survival (P =.04). The presence of at least one GST deletion proved to be an independent prognostic risk factor for response to induction treatment and overall survival in a multivariate analysis including age and karyotype (P =.02). GST genotyping was of particular prognostic value in the cytogenetically defined intermediate-risk group (P =.003). In conclusion, individuals with GSTM1 or GSTT1 deletions (or deletions of both) may have an enhanced resistance to chemotherapy and a shorter survival.     

CYP1A1, GST gene polymorphisms and risk of chronic myeloid leukemia

PRINCIPLES: Associations between polymorphisms for genes encoding enzymes involved in biotransformation of xenobiotics and susceptibility to several cancers have been shown in several studies. The aim of the present study is to investigate the influence of cytochromes P450 (CYP450) 1A1*2C and Glutathione S-transferases (GSTs) (T1 and M1) gene polymorphisms in susceptibility to chronic myeloid leukaemia (CML). METHODS: The frequency of CYP1A1 Ile/Val alleles and of GSTT1 and GSTM1 homozygous deletions was examined in 107 patients with CML and 132 healthy controls by PCR and/or PCRRFLP methods using blood samples. RESULTS: The frequency of CYP1A1 Val allele was found to be 19.2% in CML patients and 4.4% for controls, indicating that persons carrying this allele had an increased risk of CML (OR = 5.10, 95% CI: 2.60-9.97). The frequency of individuals carrying the GSTT1 null genotype was higher among CML patients (40.2%) compared to controls (19.2%) (OR = 2.82, 95% CI: 1.58-5.05; p <0.001). Therefore, GSTT1 present genotype may be a protective factor for CML. Although GSTM1 null genotype frequency was slightly higher in the patient group (44.9%) than in the controls (42.3%), this difference was not statistically significant (OR = 1.11, 95% CI: 0.66-1.86; p = 0.693). Individuals with GSTM1 null genotypes without the T allele have a 5.981 higher risk for CML than those who have the T allele. CONCLUSIONS: This data suggests that polymorphic CYP1A1 and GSTT1 genes appear to affect susceptibility to CML.     

GSTT1 and GSTM1 null genotypes may facilitate hepatitis C virus infection becoming chronic

Oxidative stress contributes to hepatitis C virus (HCV)-induced liver damage. The activity of antioxidant glutathione S-transferases (GSTs) T1 and M1 is polymorphic. The GSTT1 and GSTM1 genotypes were identified in 139 HCV-infected patients and in 329 healthy individuals. Among patients, there was an excess of GSTT1 (odds ratio [OR], 2.76 [95% confidence interval [CI], 1.77-4.30]; P<.001) and GSTM1 (OR, 1.54 [95% CI, 1.02-2.35]; P=.032) null genotypes and of double-null haplotypes (OR, 3.65 [95% CI, 1.98-6.75]; P<.001). The GSTT1 null genotype, particularly if associated with the GSTM1 null genotype, may facilitate HCV infection becoming chronic.     

GSTT1, GSTM1 and GSTP1 polymorphisms and susceptibility to juvenile idiopathic arthritis

OBJECTIVE: In this study we have analyzed GSTM1, GSTT1 and GSTP1 polymorphisms in patients with juvenile idiopathic arthritis (JIA), to investigate a possible role of these genes as genetic components of the disease. METHODS: A total of 103 individuals (49 oligoarticular, 41 polyarticular and 13 systemic) were analyzed for the three polymorphisms, using a PCR/RFLP methodology. RESULTS: We have observed significantly increased frequencies of individuals with GSTT1 null genotype in JIA patients comparing to controls (37% x 21%; p=0.0183). There was a 2-fold increased risk (OR 2.2, 95% CI 1.2-4.1) associating the disease with the GSTT1 null genotype. Considering the subgroups (oligoarticular, polyarticular and systemic), the results indicated an association between polyarticular and systemic patients and the GSTT1 null genotype. There was a 2-fold increased risk for polyarticular patients (OR 2.4, 95%, CI 1.1-5.4), and a 4-fold increased risk for systemic patients (OR 4.4, 95%, 1.3-14.5). CONCLUSION: The GSTT1 null genotype seems to be involved in polyarticular and systemic JIA.     

Role of CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 genes in the susceptibility to acute leukemias

Acute leukemias (ALs) are heterogeneous diseases. Functional polymorphisms in the genes encoding detoxification enzymes cause inter-individual differences, which contribute to leukemia susceptibility. The CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 polymorphisms in ALL (n = 156) and AML (n = 94) patients and 140 healthy controls were genotyped by PCR and/or PCR-RFLP using blood or bone marrow samples. No association was observed between the GSTT1 gene deletion and patients (OR = 0.8, 95% CI = 0.4-1.7 for AMLs and OR = 0.9, 95% CI = 0.5-1.6 for ALLs). Patients with ALL and AML had a higher prevalence of the GSTM1 deletions compared to controls but only the difference among adult AML patients (OR = 2.1, 95% CI = 1.0-4.2) was statistically significant. The CYP2D6*3 variant allele frequency was lower in the overall acute leukemia patients (0.6%) compared to controls (P = 0.03). CYP2D6*1/*3 genotype frequency also showed a protective association in AML patients (OR = 0.09, 95% CI = 0.01-1.7; P = 0.04). We also found a risk association for CYP2E1*5 in ALL and AML (OR = 3.6, 95% CI = 1.4-9.4 and OR = 3.9, 95% CI = 1.4-10.5, respectively). No association was found for the studied CYP2D6*4, CYP1A1*2A, and GSTT1"null" variants and the risk of acute leuke-mia (ALL or AML). This case-control study suggests a contribution of CYP2E1, CYP2D6, and GSTM1 "null" variants to the development of acute leukemias.     

Glutathione S-transferase M1 and T1 polymorphisms and cervical cancer risk: a meta-analysis

There were some studies on the associations between Glutathione S-transferase M1 (GSTM1) and Glutathione S-transferase T1 (GSTT1) polymorphisms and cervical cancer (CC) risk, but the results were inconsistent. Thus, a meta-analysis was performed. The electronic databases PubMed, Science Direct, CBM, and CNKI were searched for possible studies. Finally, 16 studies (1,627 cases and 2,161 controls) were included. For the GSTM1 and GSTT1 polymorphisms, the unadjusted odds ratios (OR) and 95% confidence intervals (95% CI) from each study were used to estimate summary OR. Subgroup analyses by ethnicity and histological type of CC were also performed. For the GSTM1 polymorphism, the null genotype of GSTM1 was associated with an increased CC risk in total population (OR=1.32, 95% CI=1.06-1.66). Similar association was found in Asians (OR=1.47, 95% CI=1.11-1.94), but not in Caucasians (OR=0.96, 95% CI=0.73-1.27). For the GSTT1 polymorphism, the null genotype of GSTT1 was not statistically significantly associated with CC risk in total population (OR=1.36, 95% CI=0.97-1.90). This result was also found in Asians (OR=1.27, 95% CI=0.87-1.85) and Caucasians (OR=1.09, 95% CI= 0.66-1.79), but not in Latinos (OR=4.58, 95% CI= 2.04-10.28). For the GSTM1/GSTT1 interaction analysis, the dual null genotypes of GSTM1/GSTT1 were significantly associated with increased CC risk in total population (OR=1.77, 95% CI= 1.14-2.75), and all the six studies were from Asia. For subgroup analyses by histological type of CC, the three aspects of the analyses above were all not significantly associated with CC risk in squamous cell carcinoma and adenocarcinoma, respectively. The null genotype of GSTM1 and the dual null genotypes of GSTM1/GSTT1 were risk factors in CC, and the null genotype of GSTT1 was not associated with CC risk.