Genetic Polymorphisms Of GSTP1 Research Articles

The association of combined GSTM1, GSTT1, and GSTP1 genetic polymorphisms with lung cancer risk in male Iraqi Waterpipe Tobacco (Nargila) smokers

Mutations in genes encoding proteins necessary for detoxifying oxidative stress products have been predicted to increase susceptibility to lung cancer (LC). Despite this, the association between waterpipe tobacco smoking (WP), genetic polymorphisms, and LC risk remains poorly understood. This is the first study to explore the relationship between WP tobacco smoking and these genetic factors. Previously, we investigated the association of GSTP1 SNPs (rs1695-A/G and rs1138272-C/T) with LC in Iraqi males who smoke WP. Here, we expanded our analysis to include GSTM1 (active/null) and GSTT1 (active/null) genotypes, both individually and in combination with GSTP1 SNPs. Multiplex PCR and RFLP-PCR assays were utilized to determine the genotypes of 123 cases and 129 controls. No significant association was observed between GSTM1-null or GSTT1-null genotypes and LC risk, either separately or in combination with variant genotypes of GSTP1 (rs1695 "AG+GG" and rs1138272 "CT+TT"). However, smoking WP and carrying null genotypes elevated the risk five-fold for GSTM1-null (OR 5.17, 95 % CI 2.02–13.24, P<0.001) and three-fold for GSTT1-null (OR 3.08, 95 % CI 1.55–6.13, P=0.001) compared to non-smokers carrying active genotypes. Conversely, genotype distribution analysis based on LC histological types did not indicate an increased risk of LC. Lung cancer is a complex multifactorial disease. WP smoking and GSTs genetic polymorphisms might be associated with an increased risk of developing LC. However, our data did not confirm an association between GST polymorphisms alone and the risk of LC.

Docetaxel-induced severe neuropathy, a case of breast cancer with GTSP1 polymorphism.

Breast cancer, the most prevalent cancer among women, often requires chemotherapy with docetaxel being a key agent. However, docetaxel-inducted peripheral neuropathy (DIPN) can adversely impact patients' quality of life. This case discusses an unusual instance of severe DIPN leading to wheelchair dependence in a 35-years old woman undergoing neoadjuvant treatment for locally advanced breast cancer. Following anthracycline and cyclophosphamide cycles without neurological symptoms, docetaxel administration resulted in progressive neuropathy. Despite dose reduction, the patient developed severe paraesthesias, foot weakness, and eventually wheelchair dependence. Docetaxel's microtubule-stabilizing mechanism, vital for cell division, may disrupt axonal structures, causing sensory and motor neuropathy. While rare, severe motor neuropathy, leading to wheelchair dependence, poses a significant challenge. The frequency of DIPN varies, with docetaxel exhibiting lower neuropathy rates than other taxanes. Risk factors include age, diabetes mellitus, cumulative dose, and genetic polymorphisms in GSTP1 and ABCB1. In our case, despite the patient being young, fit and without diabetes, severe DIPN occured, suggesting a potential genetic predisposition. Genetic variations, such as GSTP1 polymorphisms have been associated with DIPN. Our patient carried GSTP1 (I1e105Val) mutations, emphasizing the need for further research to establish their role as risk factors. This case underscores the importance of recognizing severe DIPN, even in atypical patient profiles. Genetic factors, like GSTP1 polymorphisms, may contribute to DIPN risk. Large-scale studies are crucial to establishing the significance of these genetic variations in DIPN susceptibility.

Genetic Polymorphisms in Glutathione S-Transferase (GST) Gene and Their Correlation with Toxicity of Chemotherapy in Breast Cancer Patients.

Glutathione S-Transferase (GST) is a family of phase II metabolizing enzymes contribute to detoxification and elimination of variety of endogenous as well as exogenous xenobiotics including chemotherapeutic agents. The comprehensive knowledge on the impact of genetic polymorphisms in GST) enzyme coding gene will help to understand the clinical outcomes in breast cancer patients treated with either Adriamycin or paclitaxel or combination of both. In this study we attempted to assess the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and their association with Adriamycin and Paclitaxel induced toxicity reactions in breast cancer patients. Two hundred BC patients receiving Adriamycin and Paclitaxel chemotherapy were enrolled in this study and chemotherapy induced hematological and non-hematological toxicity reactions were noted. The polymorphisms in GSTM1, GSTP1 and GSTT1 gene were studied by PCR and RFLP analysis. After the univariate analysis of the genetic polymorphisms of GSTM1, GSTP1 and GSTT1 showed that GSTT1 null genotype showed significant association with neutropenia (OR=2.84, 95% CI: 1.06-7.56; p=0.036) in breast cancer patients treated with Adriamycin and GSTT1 null genotype in patients with >1 CINV toxicity confirmed significant correlation (OR=3.75, 95% CI: 1.46-9.59; p=0.005). The genetic polymorphisms of GSTP1 (exon 5) A/G heterozygous genotype was significant in grade >1 toxicity reactions of mucositis (OR=3.22, 95% CI: 1.06-9.71; p=0.037) in breast cancer patients administered with Paclitaxel chemotherapy. The findings obtained from this study proposed significant involvement of GSTT1-null genotype in hematological neutropenia toxicity in response to Adriamycin and GSTM1-null genotype showed negative association with non-hematological toxicity (bodyache) in response to Paclitaxel.

Association of glutathione s-transferase pi (GSTP1) gene polymorphism in unexplained infertile women

15–20 million people in India are affected by infertility.Among them, 34% of the couples are shown to have unexplained infertility (UEI). Both genetic and environmental factors influence UEI. Data from various studies show that oxidative stress plays an important role in unexplained infertility. The genes of the phase II detoxification enzyme, Glutathione s-transferase family are upregulated in humans as a defense mechanism opposing the adverse effects of oxidative stress and play important role during pregnancy. Since all investigations for infertility work-up are normal evaluating the causes for UEI will have impact on the treatment protocol. In this study the association between GSTP1 variations and unexplained infertility are discussed. To compare the association of GSTP1 polymorphism in women with unexplained infertility and a control group.: This is a case control study with 70 normal ovulatory women who conceived within 12 months of contraceptive free intercourse, and with no history of miscarriage were recruited in the control group and 70 women with unexplained infertility were recruited as study group. All participants included in the study were between 28 and 38 years of age. The association of GSTP1 polymorphism were studied using real-time PCR with the Light Cycler instrument (Roche Applied Science).: GSTP1 variant allele frequencies were 0.39 and 0.41for control and cases respectively. The results of this study indicate GSTP1 genetic polymorphisms did not show a significant association with unexplained infertile group.

Influence of GSTM1, GSTT1, and GSTP1 genetic polymorphisms on disorders in transplant patients: a systematic review.

The glutathione-S-transferase (GST) enzymes are phase II isoenzymes responsible for protection against free radicals and xenobiotics. Since these proteins are described as polymorphic, polymorphisms in genes that encode them may alter enzymatic function and contribute to oxidative stress. In this context, such polymorphisms were already associated with several diseases and multiple therapeutic outcomes. A systematic review was performed to evaluate studies regarding the association between polymorphisms in three genes encoding enzymes of the GST family- GSTM1, GSTT1, and GSTP1- and disorders in transplant patients. A total of 125 articles on which inclusion and exclusion criteria were applied were identified at PubMed database. Thirty-two studies met the target criteria and were included in the review. The mechanisms by which GST genotypes influence the development of disorders in transplant patients differ by disorder: they may participate in it by decreasing metabolism of drugs administered to patients undergoing transplantation, then exposing them to greater toxicity; by decreasing the repair ability against oxidative stress; or by encoding proteins that may be recognized as foreign, setting of an alloimmune reaction. Although some results are better established- such as GSTM1 null genotype's role in the development of toxicity events in transplant patients- others require further evidences, as GST influence on the development of pulmonary decline and posttransplant diabetes mellitus (PTDM). The importance of investigating these associations lies in a personalized medicine, in which the high-risk genotype patient has its treatment individualized and its care for prophylaxis and surveillance increased, potentially reducing this population's morbimortality.

Features of GSTM1, GSTT1 and GSTP1 Genetic Polymorphism in Nizhny Tagil Metallurgical Plant Workers with Cardiovascular Diseases

Background: The development of cardiovascular diseases is determined not only by working conditions but also by genetic characteristics of employees. Genetic GSTM1, GSTT1 and GSTP1 variations contribute to individual differences in responses to industrial chemicals and carcinogens. Objective: To study the features of the genetic polymorphism of the GSTM1, GSTT1, and GSTP1 genes in metallurgical plant workers with diseases of the cardiovascular system in the town of Nizhny Tagil, Sverdlovsk Region, Russian Federation. Materials and methods: The case cohort included 61 men aged 33 to 61 years (mean: 48.15 ± 7.50 years), working in the converter shop and suffering from heart diseases. The control cohort consisted of 29 conditionally healthy male employees, aged 23–56, of the same iron and steel works having no signs of a cardiovascular disease. The DNA was isolated from peripheral blood using a standard technique. Deletion polymorphism of GSTM1 and GSTT1 genes was determined by quantitative PCR; Ile105Val polymorphism of the GSTP1 gene was established by qPCR using a commercial test kit. Results: We observed no statistically significant differences between the cohorts for any of the studied genes. The frequency of occurrence of the combination of GSTM1 (0/0) and GSTT1 (0/0) in the cases and controls was 14 % and 11 %, respectively, but the difference was negligible. Conclusions: Our findings demonstrate that the presence of null genotypes of GSTM1, GSTT1, as well as the mutant GSTP1 allele and the associated loss of enzyme activity contribute little to the development of cardiovascular diseases in workers exposed to occupational hazards.

Genetic polymorphisms of GSTP1, XRCC1, XPC and ERCC1: prediction of clinical outcome of platinum-based chemotherapy in advanced non-small cell lung cancer patients of Bangladesh.

Inter-individual genetic makeup can trigger variability in platinum-based chemotherapeutic responses and corresponding adverse drug reactions and toxicities. Exploring the genetic causes behind these inter-individual variabilities in platinum-based chemotherapeutic responses by investigating the effects of GSTP1 (rs1695), XRCC1 (rs25487), XPC (rs2228001) and ERCC1 (rs11615) genetic polymorphisms on toxicity and therapeutic response of this treatment among Bangladeshi advanced non-small cell lung cancer (NSCLC) patients was the aim of this study. 285 Clinically proven either stage IIIB or IV (advanced) NSCLC patients aging not less than 18years old and receiving platinum-based chemotherapy were recruited to assess the influence of these four single nucleotide polymorphisms (SNPs) on peripheral leukocytes. Toxicity and response were evaluated by multivariate regression analyses using SPSS statistical software (version 17.0). XRCC1 (rs25487) polymorphism was found to act as a predictive factor for not only grade 3 and 4 anemia (p = 0.008), neutropenia (p = 0.010), thrombocytopenia (p = 0.025) and gastrointestinal toxicity (p = 0.002) but also for therapeutic response (p = 0.012) in platinum-based chemotherapy. Although GSTP1 (rs1695) polymorphism might serve as prognostic factor regarding grade 3 or 4 neutropenia, a significant (p = 0.044) improvement in response to platinum-based chemotherapy was observed. However, XPC (rs2228001) and ERCC1 (rs11615) polymorphisms could not establish any significant relation with toxicity or therapeutic response. XRCC1 (rs2228001) and GSTP1 (rs1695) polymorphisms might explain platinum-induced clinical outcomes in terms of both toxicity and therapeutic response variations among Bangladeshi advanced NSCLC patients.

Association of Genetic Polymorphisms in GSTP1, GSTM1, and GSTT1 Genes with Vesicoureteral Reflux Susceptibility in the Children of Southeast Iran.

Background:Vesicoureteral reflux (VUR) disease is the most common type of urinary tract anomalies in children. Genetic risk factors may be associated with the etiology of VUR. The role of the Glutathione S-transferases (GSTs) as multifunctional enzymes is cellular oxidative stress handling. This is the first study aimed at evaluating the relative risk of GSTP1, GSTM1, and GSTT1 polymorphisms in VUR susceptibility in children and provides new important insights into the genetics of affected children.Methods:The study was done in 2013 in Sistan and Baluchestan University, eastern Iran. Genotyping of three GSTP1, GSTM1, and GSTT1 genes were determined using the multiplex polymerase chain reaction assay in 216 reactions for 72 VUR children and 312 reactions for 104 healthy controls.Results:The presence of GSTT1 deletion was associated with high risk of VUR in children, whereas GSTP1 and GSTM1 genotypes did not show the same effect. Furthermore, the combination of GSTT1/GSTM1 and GSTT1/ GSTP1 genotypes showed a significant influence on lower risk of VUR in children.Conclusion:Deletion of GSTT1 functional gene is a genetic risk factor causing VUR in children. Interestingly, the combination of GSTM1 and GSTP1 null genotypes with GSTT1 has shown a protective role against risk of GSTT1 deletion.

Association among genetic polymorphisms of GSTP1, HO-1, and SOD-3 and chronic obstructive pulmonary disease susceptibility.

BackgroundChronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by incomplete reversible airflow limitation, which is associated with emphysema and chronic inflammation. Oxidative/antioxidant imbalance is one of the mechanisms of the current pathogenesis of COPD and several recent studies have attempted to uncover genetic causes of COPD and its progression. GST, HO-1, and SOD-3 are important susceptibility genes related to COPD.MethodsA total of 300 blood samples were included in two groups: Control group and COPD group. We genotyped 4 single nucleotide polymorphisms (SNPs) from these 3 genes in 150 COPD patients and 150 controls to analyze genetic polymorphisms and interactions with COPD-related quantitative traits using correlation analysis and multivariate logistic regression analysis.ResultsThe results indicated that genotype distributions and allele frequencies of GSTP1, HO-1, and SOD-3 were significantly different between the COPD and the control group, while there is no correlation between the polymorphism of GSTP1, HO-1, SOD3, and the different stages of COPD. Furthermore, multivariate logistic regression analysis indicated that COPD GSTP1-exon5 SNP and HO-1 (GT)n SNP are high-risk factors for COPD and there was interaction between GSTP1 exon5 SNPS and HO-1 (GT)n SNP. More important, the genotypes, AG, GG of GSTP1 exon5 and L/M*S, L/L of HO-1 (GT)n associated with increased 8-iso-prostaglandin F (2 alpha) (8-iso-PGF2) and malondialdehyde (MDA) concentration and decreased catalase (CAT) activity.ConclusionCollectively, this study shows that genetic polymorphisms of GSTP1, HO-1, and SOD-3 are associated with COPD susceptibility.

Genetic Polymorphism of Glutathione-S-Transferase Gene (GSTP1) in Type 2 Diabetes Mellitus Patients in Basra Province/Iraq

Glutathione S-transferases (GSTs) are enzymes that included, in a wide range of detoxifying reactions by conjugation of glutathione, to electrophilic material. Polymorphisms in the genes that are responsible for GSTs affect, the function of the GSTs. GSTs play an active role in protection of cell against oxidative stress mechanism. Polymorphisms of GSTP1 at codon 105 amino acids forms GSTP1 important site for bind of hydrophobic electrophiles and the substitution of Ile/Val affect substrate specially catalytic activity of the enzyme and may correlate with reach to different diseases in human like diabetes mellitus type2 disease. Correlation between these polymorphisms and changes in the parameters file of diabetic patients has also been found, therefore, the results vary considerably among the studies. The polymerase chain reaction-restriction fragment length polymorphism was used to study GSTP1genetic polymorphism in 60 T2DM patients and 40 healthy individuals. Our results showed that presence of the GSTP1 heterozygous mutant allele Ile/Val was more common in subjects with T2DM than in the control group (35.00% and 17.50.00%, respectively. Among patients there is an association between GSTP1and the risk of T2MD, both genotypes Ile/Val and Val/Val were more prevalent which result in 2.90 and 2.58 respectively risk towards T2DM .According to Hardy–Weinberg principle there was no deviation appears in the distribution of GSTP1 Alleles. GSTP1 genotypes do not have an effect on blood lipids after infection with diabetes mellitus.

GSTM1 and GSTP1 Genetic Polymorphisms and Their Associations With Acute Lymphoblastic Leukemia Susceptibility in a Jordanian Population.

The genetic variations between different individuals in the xenobiotic detoxifying enzyme activity were shown to change susceptibility to acute lymphoblastic leukemia (ALL). The current study aimed to assess the association of GSTM1 and GSTP1 genetic polymorphisms with the susceptibility of ALL. This case-control study (N=264) involved 88 Jordanian ALL children and 176 healthy controls from an ethnically homogenous Jordanian children population. The polymerase chain reaction assay was used to genotype GSTM1 (null/present) and the polymerase chain reaction-restriction fragment length polymorphism technique was also applied to detect the genetic polymorphisms of GSTP1 (Ile105Val) at the rs1695 position. The biallelic analysis revealed that there was no association between GSTM1 double-null genotype and ALL (P=0.57). However, there was a strong association between GSTP1 (Ile105Val) polymorphism genotypes and alleles within GSTP1 gene and ALL (P=0.00049 and 0.000044, respectively). A combination between GSTM1 double-null genotype and rs1695 also showed an association with ALL (P=0.042). This study showed that the rs1695 single nucleotide polymorphism within the GSTP1 gene is strongly implicated in ALL among Jordanian children with ALL. These results indicate that genetic variants of GSTP1 gene influence the risk of developing ALL in the Jordanian children of Arab ancestry.

Lead-Related Genetic Loci, Cumulative Lead Exposure and Incident Coronary Heart Disease: The Normative Aging Study.

BackgroundCumulative exposure to lead is associated with cardiovascular outcomes. Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD), hemochromatosis (HFE), heme oxygenase-1 (HMOX1), vitamin D receptor (VDR), glutathione S-transferase (GST) supergene family (GSTP1, GSTT1, GSTM1), apolipoprotein E (APOE),angiotensin II receptor-1 (AGTR1) and angiotensinogen (AGT) genes, are believed to alter toxicokinetics and/or toxicodynamics of lead.ObjectivesWe assessed possible effect modification by genetic polymorphisms in ALAD, HFE, HMOX1, VDR, GSTP1, GSTT1, GSTM1, APOE, AGTR1 and AGT individually and as the genetic risk score (GRS) on the association between cumulative lead exposure and incident coronary heart disease (CHD) events.MethodsWe used K-shell-X-ray fluorescence to measure bone lead levels. GRS was calculated on the basis of 22 lead-related loci. We constructed Cox proportional hazard models to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CHD. We applied inverse probability weighting to account for potential selection bias due to recruitment into the bone lead sub-study.ResultsSignificant effect modification was found by VDR, HMOX1, GSTP1, APOE, and AGT genetic polymorphisms when evaluated individually. Further, the bone lead-CHD associations became larger as GRS increases. After adjusting for potential confounders, a HR of CHD was 2.27 (95%CI: 1.50–3.42) with 2-fold increase in patella lead levels, among participants in the top tertile of GRS. We also detected an increasing trend in HRs across tertiles of GRS (p-trend = 0.0063).ConclusionsOur findings suggest that lead-related loci as a whole may play an important role in susceptibility to lead-related CHD risk. These findings need to be validated in a separate cohort containing bone lead, lead-related genetic loci and incident CHD data.

The relationship between GSTA1, GSTM1, GSTP1, and GSTT1 genetic polymorphisms and bladder cancer susceptibility: A meta-analysis.

Background:Previous studies have investigated the relationship between GSTA1, GSTM1, GSTP1, and GSTT1 polymorphisms and bladder cancer (BCa) susceptibility, respectively, but the results remain inconsistent. So, we conducted this meta-analysis including 79 case–control studies to explore such relationships.Methods:We searched PubMed, EMBASE, Cochrane library, Web of Science, and CNKI for relevant available studies. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were implemented to evaluate the intensity of associations. Publication bias was estimated using Begg funnel plots and Egger regression test. To assess the stability of the results, we used sensitivity analysis with the method of calculating the results again by omitting 1 single study each time. Between-study heterogeneity was tested using the I2 statistic.Results:No significant association between GSTA1 polymorphism and BCa susceptibility (OR = 1.05, 95% CI 0.83–1.33) was noted. Besides, meaningful association between individuals who carried the GSTM1 null genotype and increased BCa risk was detected (OR = 1.39, 95%CI 1.28–1.51). When stratified by ethnicity, significant difference was found in both Caucasian (OR = 1.39, 95% CI 1.23–1.58) and Asian populations (OR = 1.45, 95% CI 1.31–1.61). Moreover, in the subgroup analysis by source of controls (SOC), the results were significant in both hospital-based control groups (OR = 1.49, 95% CI 1.35–1.64) and population-based control groups (OR = 1.21, 95% CI = 1.07–1.37). Additionally, the analysis revealed no significant association between GSTP1 polymorphism and BCa risk (OR = 1.07, 95% CI 0.96–1.20). What is more, significant associations between GSTT1 polymorphism and BCa susceptibility were discovered (OR = 1.11, 95% CI 1.00–1.22). In the subgroup analysis by ethnicity, significant associations between GSTT1 null genotype and BCa risk were observed only in Caucasians (OR = 1.25, 95% CI 1.09–1.44). Furthermore, when stratified by SOC, no obvious relationship was found between the GSTT1 null genotype polymorphism with hospital-based population (OR = 1.11, 95% CI 0.97–1.28) or population-based population (OR = 1.10, 95% CI 0.96–1.27).Conclusion:This study suggested that GSTM1 null genotype and GSTT1 null genotype might be related to higher BCa risk, respectively. However, no associations were observed between GSTA1 or GSTP1 polymorphisms and BCa susceptibility.

Association of Glutathione–S-Transferase (GSTP1) Genetic Polymorphism in Iraqi Patients with Diabetes Mellitus Type2

Glutathione S-transferases (GSTs) are enzymes that included, in a more range of detoxifying reactions by conjugation of glutathione, to electrophilic material. Polymorphisms n the genes that responsible of GSTs affect, the function of the GSTs. GSTs play an active role in protection of cell against oxidative stress mechanism. Polymorphisms of GSTP1 at codon 105 amino acids forms GSTP1 important site for bind of hydrophobic electrophiles and the substitution of Ile/Val affect substrate specially catalytic activity of the enzyme and may correlate with reach to different diseases in human like diabetes mellitus type2 disease. Correlation between these polymorphisms and changes in the parameters file of diabetic patients has also been found, therefore, the results variation considerably among the studies; therefore, these control study was designed to leading to detecting know, as there are no studies on this performed in the people of Iraq. The polymerase chain reaction-restriction fragment length polymorphism was used to study GSTP1genetic polymorphism in 60 T2DM patients and 50 healthy individuals. Our results showed that presence of the GSTP1 heterozygous mutant allele Ile/Val was more common in subjects with T2DM than in the control group (40.00% and 32.00%, respectively; p = 0.01), as well as the found of the homozygous mutant of GSTP1 allele Val/Val was common in T2DM patient and not found in the control group (3.33% and 0.00%, respectively; p = 0.001).GSTP1 genotypes do not have an effect on blood lipids after infection with diabetes mellitus. Agarose gels used to determined genotypes according to the bands were that appeared in electrophoresis of gel.

Associations of GSTM1 (del) and GSTP1 (Ile105Val) genetic polymorphisms and smoking in a family with congenital malformations

The associations of polymorphisms of the GSTM1 (del) and GSTP1 (Ile105Val) genes and smoking in a family with congenital malformations (CMs) in a newborn baby have been studied. The GSTM1 (del) and GSTP1 (Ile105Val) gene polymorphisms themselves are not associated with the risk of CMs in a newborn. However, smoking in a family may increase the risk significance of the GSTP1 (Ile105Val) genotypes in the formation of CMs in a child.

Association between CYP19A1, GSTM1, GSTT1, and GSTP1 genetic polymorphisms and the development of endometriosis in a Chinese population.

Endometriosis is a common, complicated, and highly heterogeneous endocrine disease. Many genetic factors could affect the development of endometriosis. We performed a case-control study to evaluate the association between polymorphisms in CYP19A1 rs2899470, GSTM1, GSTT1, and GSTP1 rs1695 and the development of endometriosis in a Chinese population. Between March 2014 and October 2015, 262 endometriosis patients and 275 control subjects were recruited from the Inner Mongolia Medical University. Genotyping was conducted using polymerase chain reaction-coupled with restriction fragment length polymorphism. Individuals carrying the TT genotype of CYP19A1 rs2899470 expressed a higher risk of endometriosis than those carrying the GG genotype, and the adjusted ORs (95%CI) was 2.33 (1.27-4.33). Moreover, those with the TG + TT genotype were correlated with an elevated risk of endometriosis, compared to those with the GG genotype (OR = 1.48, 95%CI = 1.03-2.13). However, GSTM1, GSTT1, and GSTP1 rs1695 polymorphisms did not affect the pathogenesis of endometriosis. In conclusion, our results suggested that CYP19A1 rs2899470 polymorphism is associated with risk for endometriosis in the Chinese population.

Glutathione-S-transferase P1 as a risk factor for Egyptian patients with chronic myeloid leukemia

Background The interest in glutathione-S-transferase (GST) isoenzymes has increased because of their regulatory role in the interaction with critical kinases involved in controlling stress response, apoptosis, and proliferation. GSTP1 is of particular interest with regard to cancer, because many tumors are characterized by high GSTP1 expression. Aim of the work We aimed at evaluating the role of GSTP1 genetic polymorphisms in chronic myeloid leukemia (CML) patients. Patients and methods We genotyped 40 CML patients and 30 healthy individuals of matched age and sex. Results Wild GSTP1 was found in 15/40 CML patients (37.5%) and in 21/30 (70%) controls, whereas mutant allele (homozygous and heterozygous) was present in 25/40 (62.5%) and 9/30 (30%) CML patients and controls, respectively. The odds ratio for GSTP1 was 3.889 (95% confidence interval, 1.417-10.674; P = 0.009*) with four-fold increased risk for CML. No significant difference in genotype frequency was present between wild and mutant genotypes when age of onset, sex, white blood cell count over 100×10 9 /l at presentation, or smoking status were considered. Conclusion These data indicate that GSTP1 mutant allele may contribute significantly to the susceptibility to CML in a sample of the Egyptian patients. These results should be considered preliminary and must be confirmed in studies with larger sample sizes.

Association of Glutathione–S-Transferase (GSTP1) Genetic Polymorphism in Iraqi Patients with Diabetes Mellitus Type2

Glutathione S-transferases (GSTs) are enzymes that included, in a more range of detoxifying reactions by conjugation of glutathione, to electrophilic material. Polymorphisms n the genes that responsible of GSTs affect, the function of the GSTs. GSTs play an active role in protection of cell against oxidative stress mechanism. Polymorphisms of GSTP1 at codon 105 amino acids forms GSTP1 important site for bind of hydrophobic electrophiles and the substitution of Ile/Val affect substrate specially catalytic activity of the enzyme and may correlate with reach to different diseases in human like diabetes mellitus type2 disease. Correlation between these polymorphisms and changes in the parameters file of diabetic patients has also been found, therefore, the results variation considerably among the studies; therefore, these control study was designed to leading to detecting know, as there are no studies on this performed in the people of Iraq. The polymerase chain reaction-restriction fragment length polymorphism was used to study GSTP1genetic polymorphism in 60 T2DM patients and 50 healthy individuals. Our results showed that presence of the GSTP1 heterozygous mutant allele Ile/Val was more common in subjects with T2DM than in the control group (40.00% and 32.00%, respectively; p = 0.01), as well as the found of the homozygous mutant of GSTP1 allele Val/Val was common in T2DM patient and not found in the control group (3.33% and 0.00%, respectively; p = 0.001).GSTP1 genotypes do not have an effect on blood lipids after infection with diabetes mellitus. Agarose gels used to determined genotypes according to the bands were that appeared in electrophoresis of gel.

Association of GSTM1 (del),GSTP1 (Ile105Val) genetic polymorphisms and smoking in the family with congenital malformations

Background. The association of GSTM1 (del) and GSTP1 (Ile105Val) polymorphisms with congenital malformations (CMs) actively studied. However, the results of various studies are conflicting. This study aims to investigate the association of GSTM1 (del), GSTP1 (Ile105Val) genetic polymorphisms and smoking in the family with congenital malformations in the newborn. Method. We studied 94 newborn with CMs and 125 healthy newborn. Null genotype of GSTM1 was identified through multiplex real-time PCR, and GSTP1 gene (Ile105Val) polymorphism was determined through TaqMan-real-time PCR. Results. The study showed that polymorphic loci of GSTM1 (del) and GSTP1 (Ile105Val) genes were not associated with the risk of congenital malformations in the newborn (P = 0,46 and P = 0,47). When comparing the frequencies of genotypes the GSTP1 (Ile105Val) gene in newborn with CMs in the families of smokers with those of healthy newborn in non-smoking families statistically significant differences between them were found (P = 0,02). The genotype Ile/Val in children was associated with CMs (ORg + f = 2,59; 95 % CI: 1,05- 6,35), while the homozygous genotype Ile/Ile in newborn was associated with a protective effect to CMs (ORg + f = 0,30; 95 % CI: 0,12-0,72). Possibly, the association of the homozygous genotype Val/Val did not reach statistical significance due to a small number of children surveyed. Conclusion. The smoking in the family increases the risk of CMs in the newborn with genotypes of GSTP1 gene (Ile105Val) polymorphism.

Pharmacogenetic association between GSTP1 genetic polymorphism and febrile neutropenia in Japanese patients with early breast cancer.

Genetic risk factors for febrile neutropenia (FN), the major adverse event of perioperative chemotherapy for early breast cancer, remain unclear. This study retrospectively explored pharmacogenetic associations of single nucleotide polymorphisms (SNPs) of the uridine glucuronosyltransferase 2B7 (UGT2B7, rs7668258), glutathione-S-transferase pi 1 (GSTP1, rs1695), and microcephalin 1 (MCPH1, rs2916733) genes with chemotherapy-related adverse events in 102 Japanese women who received epirubicin and cyclophosphamide as perioperative chemotherapy for early breast cancer. The allele frequencies for all of the SNPs were in concordance with the Hap-Map data of Japanese individuals. Among the 24 patients who had FN at least once during all courses of chemotherapy, 23 had the A/A genotype, and 1 had the A/G genotype of the GSTP1 polymorphism (rs1695, P=0.001); 23 of the 70 patients with the A/A genotype had FN, as compared with only 1 of the 32 patients with the A/G and G/G genotypes. The genotype distributions of the UGT2B7 and MCPH1 polymorphisms did not differ between the patients who had FN or grade 3/4 neutropenia and those who did not. Among Japanese women who received epirubicin and cyclophosphamide as perioperative chemotherapy for early breast cancer, those with the A/A genotype of the GSTP1 polymorphism (rs1695) were more likely to have FN.