Glutathione S-Transferase Enzyme (GSTT1 and GSTM1) Gene Polymorphisms and Oxidative Stress in Egyptian Patients with End Stage Renal Disease.

Glutathione S-transferase enzyme (GSTT1 and GSTM1) gene polymorphisms have been associated with the genetic susceptibility to end stage renal disease (ESRD) in different populations. We investigated the association between GSTT1 and GSTM1 genes, and ESRD in Egyptian population. The samples of 133 ESRD and 91 control subjects were collected, and their clinical characteristics were assayed. Glutathione S-transferase enzyme (GSTT1 and GSTM1) gene polymorphisms were detected by polymerase chain reaction (PCR). Serum level of malondialdehyde (MDA), the oxidative stress and lipid peroxidation biomarker, and plasma glutathione S-transferase enzyme (GST), the antioxidant enzyme, were estimated in the ESRD patients as well as in the control subjects. We demonstrated the association of MDA and GST enzyme levels with GSTT1 and GSTM1 genotypes. We investigated the association between MDA and lipid parameters in the ESRD patients. Increased of the GSTM1 deletion genotype, (GSTT1/0) and both deletion genotypes (0/0) in the ESRD patients when compared with the control subjects (P < 0.0001, OR = 3.786, 95% CI = 2.151-6.664), (P = 0.001, OR = 3.172, 95% CI = 1.595-6.308) and (P = 0.045, OR = 1.945, 95% CI = 1.009-3.749), respectively. Highly significant increase of MDA level in the ESRD patients as compared with the control subjects (P < 0.0001). Highly significant decrease of GST enzyme level in the ESRD patients as compared with the control subjects (P < 0.0001).The level of MDA is significantly increased in all GST genotypes in the ESRD patients as compared with the control group. Also, there were significant association between The genetic risk factors of GSTT1 and GSTM1 genes in the ESRD, and high level of MDA in the ESRD patients, while the level of GST enzyme is significantly decreased in GST genotypes except the both deletion (0/0) genotypes, in which the level of GST enzyme is not significantly decreased in the ESRD patients as compared with the control subjects. There are significant association between the genetic risk factors of GSTT1 and GSTM1 genes in the ESRD, (GSTM1 null and GSTT1/0 genotypes), and low level of GST enzyme in the ESRD patients. There were significant positive correlation between MDA and total cholesterol, triglyceride, and LDL-cholesterol, and significant negative correlation between MDA and HDL-cholesterol in the ESRD patients as compared with the control subjects. In conclusion, the GSTM1 (null) genotype, (GSTT1/0) and (0/0) genotypes are independent risk factors for ESRD. The oxidative stress and lipid abnormalities are associated with ESRD in the studied Egyptian population.

Glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genetic polymorphisms and atopic asthma in children from Southeastern Brazil

Xenobiotics can trigger degranulation of eosinophils and mast cells. In this process, the cells release several substances leading to bronchial hyperactivity, the main feature of atopic asthma (AA). GSTM1 and GSTT1 genes encode enzymes involved in the inactivation of these compounds. Both genes are polymorphic in humans and have a null variant genotype in which both the gene and corresponding enzyme are absent. An increased risk for disease in individuals with the null GST genotypes is therefore, but this issue is controversial. The aim of this study was to investigate the influence of the GSTM1 and GSTT1 genotypes on the occurrence of AA, as well as on its clinical manifestations. Genomic DNA from 86 patients and 258 controls was analyzed by polymerase chain reaction. The frequency of the GSTM1 null genotype in patients was higher than that found in controls (60.5 percent versus 40.3 percent, p = 0.002). In individuals with the GSTM1 null genotype the risk of manifested AA was 2.3-fold higher (95 percentCI: 1.4-3.7) than for others. In contrast, similar frequencies of GSTT1 null and combined GSTM1 plus GSTT1 null genotypes were seen in both groups. No differences in genotype frequencies were perceived in patients stratified by age, gender, ethnic origin, and severity of the disease. These results suggest that the inherited absence of the GSTM1 metabolic pathway may alter the risk of AA in southeastern Brazilian children, although this must be confirmed by further studies with a larger cohort of patients and age-matched controls from the distinct regions of the country.

Glutathione S-Transferase M1 Polymorphism and Schizophrenia / 신경정신의학

OBJECTIVES: This study aimed to test the possible association between Glutathione S-Transferase M1 gene (GSTM1) variants and schizophrenia. METHODS: One hundred and eleven inpatients with schizophrenia and 130 healthy controls were recruited. Genotyping was performed by polymerase chain reaction-based method. RESULTS: The GSTM1 null genotype was significantly more frequent in patients with schizophrenia than in controls (p=0.014, odd ratio=1.93, 95% confidence interval=1.115-3.351), while GSTM1 genotype variants were not associated with either tardive dyskinesia (TD) or total Abnormal Involuntary Movement Scale (AIMS) scores. CONCLUSION: The present study suggests that the GSTM1 polymorphism may confer susceptibility to the development of schizophrenia but not to TD, at least in Korean population.

Relationship between Glutathione S Transferase M1 Gene Polymorphism and Endometriosis / 대한산부인과학회잡지

OBJECTIVE: To investigate the relationship between glutathione S-transferase M1 (GSTM1) gene polymorphism and endometriosis in Korean women. METHODS: The GSTM1 gene polymorphism was analyzed by GSTM1-specific polymerase chain reaction (PCR) and nested PCR in 62 patients with endometriosis and 99 normal control women. RESULTS: There was no significant difference in the frequency of the GSTM1 gene deletion between patients with endometriosis (64.5%) and normal control women (60.6%). Also, this frequency in early stage endometriosis was similiar to that in late stage endometriosis. The distribution of active GSTM1 genotype in patients with endometriosis was not different from that in normal control women. No significant difference in the distribution of active genotype was noted between early stage endometriosis and late stage endometriosis. CONCLUSION: The GSTM1 gene polymorpjhism is not related with endometriosis in Korean women.

Gene Polymorphism to the Effects of Low Level Aromatic Solvents Exposure on Spontaneous Abortion / 环境与健康杂志

Objective To investigate the association between genetic polymorphisms of cytochrome P450 MSP1 gene and the glutathione s-transferase GSTM1 gene in female workers exposed to aromatic solvents and spontaneous abortion. Methods A retrospective epidemiological investigation was carried out among 276 female workers including 58 female workers with history of spontaneous abortion and 218 female workers without spontaneous abortion selected in Yanshan of Beijing by the trained investigators using the unified questionnaire. Results The spontaneous abortion of female workers was significantly associated with GSTM1 (absent) (OR=2.07, 95% CI: 1.15-3.71), but not MSP1 (present) and exposure to aromatic solvent. After adust-ment for major confounders including education, age, shift work, body mass index, passive smoking and occupational stress, the multiple logistic regression analysis showed that GSTM1 gene (absent) significantly increased the risk of spontaneous abortion of female workers (OR=2.15, 95% CI: 1.17-3.98). Before and after adjustment for major confounders including education, age, shift work, body mass index, passive smoking and occupational stess, the multiple regression analysis showed that GSTM1 (absent) combined with MSP1 (heterozygous variant type / homozygous variant type) significantly increased the risk of spontaneous abortion (OR=2.98, 95% CI:l. 17-7.59), using the group with GSTM1 (present) and MSP1 (homozygous wild type) as reference group. Conclusion Our data suggested a genetic influence on spontaneous abortion in this population, GSTM1 (absent) was significantly associaled with spontaneous abortion, also provide evidence of additional joint action of gene MSP1 (heterozygous variant type and homozygous variant type) and GSTM1 (absent) to spontaneous abortion.