GSTM1 Null Polymorphism Research Articles

Null polymorphism of the GSTM1 and GSTT1 genes in susceptibility to colorectal tumorigenesis: systematic review with meta-analysis

Objective: To assess if GSTT1 and GSTM1 null polymorphisms increase susceptibility to colorectal cancer. Methods: A search was conducted in PubMed, SciELO, BVS, and Medline databases. Forty articles were selected, totaling 12,698 cases and 19,517 controls. Odds ratios with 95% confidence intervals were used, and p-values <0.05 were considered significant. The Dersimonian-Laird method was applied for p-values <0.05, and the Mantel-Haenszel method was used otherwise. All p-values were two-tailed with an alpha value of 0.05 determined a priori. STATA 16.0 software was utilized. Result: A higher risk of colorectal cancer was shown in the general population for the GSTM1 null genotype (OR=1.11; 95%CI [1.03, 1.19]; P<0.01). No significant risk was observed for GSTT1 or the GSTM1/GSTT1 null combination (OR=1.09; 95%CI [0.98, 1.22]; P<0.01 and OR=1.13; 95%CI [0.89, 1.43]; P<0.01, respectively). In subgroup analysis, increased colorectal cancer risk was found for Asians with the GSTM1 null genotype (OR=1.10; 95%CI [1.02, 1.20]; P=0.02) and GSTM1/GSTT1 null combination (OR=1.49; 95%CI [1.03, 2.15]; P<0.01). Conclusion: The findings suggest that the GSTM1 null polymorphism and the GSTM1/GSTT1 null combination are potential susceptibility factors for colorectal cancer, particularly in the Asian population.

Association of mRNA expression and polymorphism of antioxidant glutathione-S-transferase (GSTM1 and GSTT1) genes with the risk of Gestational Diabetes Mellitus (GDM)

Gestational Diabetes Mellitus (GDM) is a medical complication during the gestational period in which woman who had never been diagnosed with diabetes develops hyperglycemia. Prior studies have demonstrated that the advancement of GDM and its consequences arises from a disparity between oxidants and antioxidants in the cells. The observed outcomes can be attributed to an excessive formation of reactive oxygen species (ROS) within the cells, coupled with a reduced activity of anti-oxidative enzymes. Glutathione S-transferase (GSTs) is recognized as an antioxidant enzyme that is belong to as a phase II family member of detoxifying enzymes. These metabolic multigene catalysts are found into the cytoplasm of the cell. GSTs play a vital part in the elimination of cellular ROS or free radicals. The study involves total 300 pregnant women, (150 GDM cases and 150 healthy controls). The polymorphism study of GSTs genes (GSTM1 and GSTT1) was determined by conventional Polymerase Chain Reaction (PCR). The mRNA expression study of GSTM1 and GSTT1 genes analysed by qPCR/ RT-PCR (quantitative PCR/Real-Time PCR) followed by statistical analysis done using Prism8 software (version 8.01). The study revealed statistically significant variations in biochemical parameters between GDM cases and controls. It was found GSTM1-null (GSTM1-/-) polymorphism significantly (P < 0.0001) most prevalent in GDM cases (56.7%) when compared to healthy control (28%). However, no significant difference was observed for GSTT1 null and present polymorphism (P = 0.906). The gene expression levels of both GSTM1 and GSTT1 were found considerably downregulated in individuals with GDM as compared to the control group (P < 0.0001). The downregulation of gene expression has a significant (P<0.0001) association with the null/deletion polymorphism of both GSTM1/ GSTT1 genes respectively. Null/deletion genotype of GSTM1 gene and its expression showed significant association with GDM. Therefore, this gene variant has the potential to be used as a prognostic biomarker for GDM. However, there is need to study this gene variant in larger sample size and different ethnicity.

Influence of genetic polymorphisms of Hg metabolism and DNA repair on the frequencies of micronuclei, nucleoplasmic bridges, and nuclear buds in communities living in gold mining areas

Fishing communities living near gold mining areas are at increased risk of mercury (Hg) exposure via bioaccumulation of methylmercury (MeHg) in fish. This exposure has been linked to health effects that may be triggered by genotoxic events. Genetic polymorphisms play a role in the risk associated with Hg exposure. This study evaluated the effect of single nucleotide polymorphisms (SNPs) in metabolic and DNA repair genes on genetic instability and total hair Hg (T-Hg) levels in 78 individuals from "La Mojana" in northern Colombia and 34 individuals from a reference area. Genetic instability was assessed by the frequency of micronuclei (MNBN), nuclear buds (NBUDS), and nucleoplasmic bridges (NPB). We used a Poisson regression to assess the influence of SNPs on T-Hg levels and genetic instability, and a Bayesian regression to examine the interaction between Hg detoxification and DNA repair. Among exposed individuals, carriers of XRCC1Arg399Gln had a significantly higher frequency of MNBN. Conversely, the XRCC1Arg194Trp and OGG1Ser326Cys polymorphisms were associated with lower frequencies of MNBN. XRCC1Arg399Gln, XRCC1Arg280His, and GSTM1Null carriers showed lower NPB frequencies. Our results also indicated that individuals with the GSTM1Nulland GSTT1null polymorphisms had a 1.6-fold risk for higher T-Hg levels. The Bayesian model showed increased MNBN frequencies in carriers of the GSTM1Null polymorphism in combination with XRCC1Arg399Gln and increased NBUDS frequencies in the GSTM1Null carriers with the XRCC3Thr241Met and OGG1Ser326Cys alleles. The GSTM1+ variant was found to be a protective factor in individuals carrying OGG1Ser326Cys (MNBN) and XRCC1Arg280His (NPB); the GSTT1+ polymorphism combined with XRCCArg194Trp also modulated lower MNBN frequencies, while GSTT1+ carriers with the XRCC1Arg399Gln allele showed lower NPB frequencies. Consistent with GSTM1, GSTT1Null carriers with XRCC3Thr241Met showed increased NBUDS frequency. With the rise of gold mining activities, these approaches are vital to identify and safeguard populations vulnerable to Hg's toxic effects.

Genomic Pattern of GSTM1 and T1 Gene Null polymorphism of Head and Neck Cancer Patients in Eastern India.

Homozygous deletion i.e., null polymorphism of the Glutathione S transferases genes hinders detoxification reactions by altering the sensitization of glutathione s transferases enzymes. Hence, we analysed the association between the GSTM1 and GSTT1 gene polymorphisms and head and neck cancer (HNC). The study consists of 238 healthy controls and 160 diagnosed cases of HNC, who attended the Regional Cancer Centre, Indira Gandhi Institute of Medical Sciences (a tertiary care hospital). DNA was extracted from whole blood of patients and control using Qiagen DNA extraction kit. GSTM1 and GSTT1 gene polymorphisms were examined using PCR and agarose gel electrophoresis. GSTM0 null polymorphism was 26.25% and 15.13% in cases and control respectively. GSTT0 null polymorphism was observed in 18.13% cases and 8.82% in control groups. The GSTM0 null polymorphism was present significantly in case group as compared to control group (OR = 1.997, p = 0.006). There was also significant association of GSTT0 null polymorphism with case group as compared to control group (OR = 2.288, p = 0.006). The combined genotypes were also analysed. GSTM0T1 genotype (n = 27) was found to be most common among HNC group followed next by GSTM0T0 double deletion (n =15). The result indicated that there was strong association of GSTM0 and GSTT0 null polymorphism in those patients. The combined genotypes i.e., GSTM0T1 and GSTM0T0 null polymorphism also showed significant association in HNC patients.

Increased Risk of Acute Lymphoblastic Leukemia in Adult Patients with GSTM1 Null Genetic Polymorphism.

PurposeGlutathione S-transferases (GSTT1 and GSTM1) detoxify various endogenous and exogenous compounds and provide cytoprotective role against reactive species. This study aimed to assess the frequency of GSTT1, and GSTM1 polymorphisms in newly diagnosed Sudanese adult patients with acute lymphoblastic leukemia (ALL) and to evaluate the association of these polymorphisms with age, gender and type of ALL.Patients and MethodsThis case–control study included 128 adult Sudanese, untreated newly diagnosed patients with ALL, aged 18 to 74 years and 128 age-gender matched healthy controls. Deletional polymorphisms of GSTT1 and GSTM1 genes were genotyped through a multiplex polymerase chain reaction (PCR) assay using β-globin gene as an internal positive control.ResultsThe genotypic frequency of GSTT1 null polymorphism was 22.7% in cases and 14.8% in controls (OR = 1.68, P = 0.111). Statistically significant differences were noted in the frequencies of GSTM1 null polymorphism in cases and controls (OR = 3.7, P = <0.001). Combined GSTT1 null and GSTM1 null gene polymorphisms showed statistically significant difference in patients with ALL as compared to controls (OR = 6.5, CI 95% = 1.42–29.74, P < 0.001).ConclusionIrrespective of age at diagnosis, gender, and phenotype of ALL, GSTM1 null polymorphism either alone or in combination with GSTT1 null polymorphism poses significantly increased risk of developing ALL in adults.

Susceptibility of Glutathione-S-Transferase Polymorphism to CVD Develo- pment in Type 2 Diabetes Mellitus - A Review.

Metabolic disorder affects normal homeostasis and can lead to the development of diseases. Diabetes mellitus is the most common metabolic disorder, and a cluster of metabolic conditions can lead to cardiovascular disease (CVD) development. Diabetes mellitus and CVD are closely related, with oxidative stress, playing a major role in the pathophysiology. Glutathione-S-Transferases (GST) potentially play an important role by reducing oxidative stress and is found to be the underlying pathophysiology in the development of diabetes, cardiovascular diseases (CVD), etc Background: In this review, the role of GST genetic variant in the development of diabetes mellitus, CVD and diabetic vascular complications has been focused. Objectives: Based on the literature, it is evident that the GST can act as an important biochemical tool providing significant evidence regarding oxidative stress predominant in the development of diseases. Analysis of GST gene status, particularly detection of GSTM1 and GSTT1 null mutations and GSTP1 polymorphism, have clinical importance. Results: The analysis of GST polymorphism may help identify the people at risk and provide proper medical management. Genotyping of GST gene would be a helpful biomarker for early diagnosis of CVD development in DM and also in CVD cases. More studies focusing on the association of GST polymorphism with CVD development in diabetic patients will help us determine the pathophysiology better.

Combined GSTT1 Null, GSTM1 Null and XPD Lys/Lys Genetic Polymorphisms and Their Association with Increased Risk of Chronic Myeloid Leukemia.

PurposeGlutathione S-transferases (GSTT1 and GSTM1) are instrumental in detoxification process of activated carcinogens. Nucleotide excision repair is carried out by DNA helicase encoded by xeroderma pigmentosum group D (XPD) genes and aberrations in the XPD gene predisposes to increased risk of cancer. The present study aimed to investigate GSTT1, GSTM1 and XPD polymorphisms in newly diagnosed chronic myeloid leukemia (CML) patients and to examine the association of these polymorphisms with the risk of developing CML.Patients and MethodsThis case–control study was carried out from June 2019 to August 2021 involving 150 newly diagnosed patients with CML and an equal number of randomly selected age- and sex-matched healthy individuals. A multiplex-PCR assay was used to genotype GSTT1 null and GSTM1 null polymorphisms. XPD gene polymorphism was detected by PCR-RFLP using predesigned gene-specific primers.ResultsGSTT1 and GSTM1 null polymorphisms were detected in 42.7% and 61.3% of cases, respectively, compared to 18% and 35.3% for controls. The combination of both GST null polymorphisms revealed a significant association with CML. Frequencies of XPD Lys751Gln genotypes in cases were 62.7% heterozygous Lys/Gln, 24% homozygous Lys/Lys and 13.3% homozygous Gln/Gln, while in the controls were 74.7%, 20%, and 5.3%, respectively. Significant differences were also noted regarding the combination of GSTT1/GSTM1 null with XPD Lys/Lys, and GSTM1 null with XPD Lys/Lys.ConclusionIn conclusion, GSTT1 null, GSTM1 null and XPD polymorphisms showed positive association with the risk of development of CML. Furthermore, age and gender did not exhibit any association with the studied polymorphisms, while CML phases were associated with GSTT1 null polymorphism.

The Cumulative Effect of Gene-Gene Interactions Between GSTM1, CHRNA3, CHRNA5 and SOD3 Gene Polymorphisms Combined with Smoking on COPD Risk.

BackgroundChronic obstructive pulmonary disease (COPD) is a multifactorial disorder which is affected by external and internal risk factors. People with no external risk factors may be significantly affected and develop pulmonary disease. The study aimed to define gene–gene and gene–environmental effects on COPD.MethodsA case control study involved 181 COPD patients and 292 healthy individuals, with peripheral blood sampling and adequate questionnaires. Genotyping was done with various types of PCR design for GSTM1 (null del), GSTT1 (null del), EPHX1 (rs2234922 and rs1051740), GSTP1 (rs1695 and rs1138272), CHRNA3 (rs1051730 and rs12914385), CHRNA5 (rs16969968 and rs17486278), and SOD3 (rs1799895 and rs699473) gene polymorphisms. Gene–gene and gene–environmental interactions were investigated using multidimensional regression analysis.ResultsFrequency of risk alleles of rs1051730 (p = 0.001), rs16969968 (p <0.001), and rs1799895 (p <0.001) polymorphisms were significant in univariate analysis. For gene–gene interaction, GSTM1 null, rs1051730, rs16969968, and rs1799895 polymorphisms independently contributed to risk of COPD and any combinations of the risk genotypes have a higher risk of disease. A cumulative effect of the four risk polymorphisms increased the risk of COPD for the smoking index (cOR = 13.6, p <0.001), cigarettes per day (cOR = 32.08, p <0.01), nicotine dependence (cOR = 12.0, p <0.01), and smoking status (cOR = 17.02, p <0.01) for gene–environmental interaction.ConclusionSeveral pivotal genes showed distinct effects for COPD, and some synergistic effects affected the disease progression. The development of COPD was synergistically increased with gene–gene and gene–environmental risk factors.

Influence of genetic polymorphisms in glutathione-S-transferases gene in response to imatinib among Brazilian patients with chronic myeloid leukemia

Polymorphism in metabolizing enzymes can influence drug response as well as the risk for adverse drug reactions. Nevertheless, there are still few studies analyzing the consequence of polymorphisms for the Glutathione-S-transferases (GST) gene to drug response in chronic myeloid leukemia (CML). This study reports, the influence of GSTP1*B and GSTT1/GSTM1null polymorphisms in response to imatinib in CML patients in a Brazilian population. One hundred thirty-nine CML patients from the Clinical Hospital of Goiânia, Goiás, Brazil, treated with imatinib were enrolled in this study. Genotyping of GSTT1 and GSTM1 genes deletions were performed by qPCR and of GSTP1 gene was performed by RFLP-PCR. The frequency of GSTP1*1B, GSTT1 and GSTM1null polymorphisms were determined for all patients. The influence of each patient's genotypes was analyzed with the patient's response to imatinib treatment. Brazilian CML patients revealed GSTT1 and GSTM1 genes deletions. GSTT1 deletion was found in 19.3% of patients and GSTM1 deletion in 48.7% of patients with CML. GSTT1/GSTM1 deletion was found in 11.7% in Brazilian CML patients. The "G allele" of GSTP1*B, is associated with later cytogenetic response in imatinib therapy. While, the gene presence combined with GG genotype (GSTM1 present/GSTPI-GG) conferred a tend to a later cytogenetic response to patients. GSTP1*B and GSTT1/GSTM1null polymorphisms influence treatment response in CML. Brazilian CML patients presenting GSTP1 AA/AG genotypes alone and in combination with GSTT1 null reach the cytogenetic response faster, while patients presenting GSTP1-GG and GSTMI positive genotypes may take longer to achieve cytogenetic response. As a result, it allows a better prognosis, with the use of an alternative therapy, other than reducing treatment cost.

Influence of Estrogenic Metabolic Pathway Genes Polymorphisms on Postmenopausal Breast Cancer Risk.

Estrogen metabolism plays an important role in tumor initiation and development. Lifetime exposure to high estrogens levels and deregulation of enzymes involved in estrogen biosynthetic and metabolic pathway are considered risk factors for breast cancer. The present study aimed to evaluate the impact of mutations acquisition during the lifetime in low penetrance genes that codify enzymes responsible for estrogen detoxification. Genotype analysis of GSTM1 and GSTT1 null polymorphisms, CYP1B1 Val432Leu and MTHFR C677T polymorphisms was performed in 157 samples of women with hormone-dependent breast cancer and correlated with the age at diagnosis. The majority of patients with GSTT1 null genotype and with both GSTM1 and GSTT1 null genotypes were 50 years old or more at the diagnosis (p-value = 0.021 and 0.018, respectively). Older women with GSTM1 null genotype were also carriers of the CYP1B1Val allele (p-value = 0.012). As well, GSTT1 null and CYP1B1Val genotypes were correlated with diagnosis at later ages (p-value = 0.022). Similar results were found associating MTHFR C677T and GSTT1 null polymorphism (p-value = 0.034). Our results suggest that estrogen metabolic pathway polymorphisms constitute a factor to be considered simultaneously with models for breast cancer risk assessment.

Association of GSTM1 and GSTT1 Null Deletions and GSTP1 rs1695 Polymorphism with the Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis

Context: Hepatocellular carcinoma (HCC), as the most common type of primary liver cancer (accounting for 70% - 90% of all liver cancers), is the seventh most common malignancy worldwide. Glutathione S-transferases (GSTs) are a specific group of enzymes that are responsible for the detoxification of carcinogens. According to the available literature, genetic variations in this group of enzymes may be associated with the risk of HCC. In this study, we aimed to assess the association of GSTM1 and GSTT1 null deletions and GSTP1 rs1695 polymorphism with the risk of HCC. Methods: We systematically searched electronic databases, including PubMed, Scopus, and Web of Science, using appropriate keywords to gather relevant data until March 2019. Studies that met the inclusion criteria were included in the meta-analysis, using either fixed- or random-effects models based on the presence of heterogeneity. Results: This meta-analysis pooled 19 studies for GSTM1 null deletions, 14 studies for GSTT1 null deletions, and five studies for GSTP1 rs1695 polymorphism. In terms of heterogeneity, the pooled odds ratio (OR) was calculated in a random-effects model for both Asian and non-Asian populations. HCC was found to be associated with GSTM1 null deletions (OR = 1.26, 95% CI: 1.00 - 1.58, P = 0.05) and GSTT1 null deletions (OR = 1.39, 95% CI: 1.10 - 1.74, P = 0.005); however, no significant association was found between HCC and GSTP1 rs1695 polymorphism (OR = 1.14, 95% CI: 0.86 - 1.50, P = 0.36). Conclusions: We found that GSTM1 and GSTT1 null deletions increased the risk of HCC; however, the GSTP1 rs1695 polymorphism did not have a similar effect.

GSTM1 null polymorphism and palmar dermatoglypics in oral leukoplakia.

An individual's risk towards development of cancer depends not only on environmental factors or extrinsic exposure to carcinogens but also on individual's genetic susceptibility. To determine two genetically established parameters such as prevalence of GSTM1 null polymorphism and analysis of Palmar dermatoglypics (PD) in patients with Oral Leukoplakia (OL) and Controls. Group I (cases) 30 patients with established histopathological diagnosis of OL and Group II (controls) 30 patients without any habits of tobacco, alcohol usage and without OL were selected. After informed consent, the palm prints were recorded using a Canon PIXMA MP250 scanner and 2 ml of blood was collected and transported under cold cycle and taken for evaluation of GSTM1 null polymorphism using Multiplex PCR. There exists a highly significant difference in GSTM1 null polymorphism (p-0.002), Finger ridge patterns (arches- p-0.027, loops p-0.001, whorls p-0.001), hypothenar pattern (p-0.015), ATD angle (p-0.001), AB count (p-0.007) between cases and controls. Similarly, when analysing the GSTM1 null polymorphism with PD among cases, there exists a significant association between loops (p-0.001), AB count (p-0.058) and hypothenar pattern (p-0.076), respectively 43% of OL cases had alteration in both which implies that those patients are at a higher risk of developing cancer. Not all patients who smoke or chew tobacco develop cancer. This could probably be due to the individual's genetic susceptibility. Environment gene interactions, in the form of GSTM1 polymorphism, and carcinogenesis, share links that can help in the prediction of risk for oral cancer development, and use of such markers can aid in prediction of oral cancer susceptibility in exposed individuals. Palm prints once formed do not change throughout life and are not influenced by environment. It can also serve as genetic markers to predict the risk of occurrence of oral cancer.

Glutathione S-transferase gene polymorphisms (GSTT1 and GSTM1) and risk of schizophrenia: A case-control study in Chinese Han population.

Schizophrenia (SCZ) is a chronic disability disorder related to oxidative stress. Glutathione S-transferase (GST) is a group enzyme that protects cells and tissues from oxidative stress damage. Among GSTs, GSTT1 and GSTM1 have well defined genetic polymorphisms. The purpose of our research was to explore the correlation between GSTT1 and GSTM1 polymorphism and SCZ risk in Chinese Han population.A total of 650 subjects (386 SCZ patients and 264 healthy individuals) were included in this case–control designed study. The GSTT1 and GSTM1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR). We explored the relationship between these 2 polymorphisms and the risk of SCZ.We found that the GSTT1 null genotype had a protective effect on the development of SCZ [odds ratio (OR) = 0.601, 95% confidence interval (95% CI) = 0.412–0.986, P = .031]. We also found that the combination of null genotypes of the GSTT1 and GSTM1 genes was made at a lower risk of SCZ (OR = 0.452, 95% CI = 0.238–0.845, P = .028). However, we found no correction between Positive and Negative Syndrome Scale score (PANSS) and GSTM1, GSST1 genotypes in SCZ patients.Our finding revealed that GSTT1 null polymorphisms may be related to the reduced risk of SCZ in Chinese Han population, and this risk was further reduced with the combination of GSTT1 null polymorphisms and GSTM1 null polymorphisms.

GST null polymorphisms may affect the risk of coronary artery disease: evidence from a meta-analysis

BackgroundWhether glutathione S-transferase (GST) null polymorphisms, namely GSTM1 null, GSTP1 null and GSTT1 null polymorphisms, influence the risk of coronary artery disease (CAD) or not remains unclear. Thus, the authors performed a meta-analysis to more robustly estimate associations between GST null polymorphisms and the risk of CAD by integrating the results of previous publications.MethodsMedline, Embase, Wanfang, VIP and CNKI were searched comprehensively for eligible studies, and 45 genetic association studies were finally selected to be included in this meta-analysis.ResultsWe found that GSTM1 null polymorphism was significantly associated with the risk of CAD in overall population (OR = 1.37, p = 0.003) and mixed population (OR = 1.61, p = 0.004), GSTP1 null polymorphism was significantly associated with the risk of CAD in overall population (OR = 1.23, p = 0.03), whereas GSTT1 null polymorphism was significantly associated with the risk of CAD in overall population (OR = 1.23, p = 0.02), Caucasians (OR = 1.23, p = 0.02) and East Asians (OR = 1.38, p < 0.0001).ConclusionsThis meta-analysis demonstrated that GSTM1 null, GSTP1 null and GSTT1 null polymorphisms were all significantly associated with an increased risk of CAD.

Genotype of Null Polymorphisms in Genes GSTM1, GSTT1, CYP1A1, and CYP1A1*2A (rs4646903 T>C)/CYP1A1*2C (rs1048943 A>G) in Patients with Larynx Cancer in Southeast Spain.

Simple SummaryEpidemiological studies have shown that individual susceptibility to cancer is mediated by genetic and environmental factors. The aim of the present study is to evaluate the individuals’ metabolic genetic susceptibility to toxic habits (smoking and alcohol consumption) by detecting polymorphisms CYP1A1 rs1048943 T>C and CYPA1A2 rs4646903 A>G, and null polymorphisms in GSTM1 and GSTT1 genotypes, comparing a group of healthy control subjects with a population of larynx cancer patients from southeastern Spain. As results patients with larynx cancer present more gene GSTM1 and GSTT1 null polymorphisms, and CYP1A1 rs4646903 T>C polymorphisms.Background: some types of cancer have been associated with the presence of single nucleotide polymorphisms (SNPs) of some genes that encode enzymes: glutathione-S transferase (GST), whose alteration leads to loss of function and a lower capacity to eliminate toxic GSTM1 and GSTT1 null genotypes; SNPs causing loss of function of CYP1A1 or CYP1A1–2 cytochrome P450 enzymes related with a lower capacity to deactivate hydrocarbons related to smoking, which involves a higher risk of developing some smoking-dependent cancers including larynx cancer. Objective: to compare the presence of null SNPs in genes GSTM1, GSTT1, and CYP1A1 rs 4646903 T>C, and CYP1A1–2 RS1048943 A>G in patients with hypopharyngeal and larynx cancer with a healthy control group. Materials and method: The study included a total of 80 patients with hypopharyngeal and laryngeal cancer and 23 healthy subjects. Genomic DNA was obtained from saliva samples, determining genotype GSTM1 (present +, or null −), GSTT1 (present + or null −). Polymorphisms (SNP) in CYP1A1 T>C (present + CC, or absent − TC/TT), and CYP1A1–2 A>G (present + GG, or absent − AG/AA). Results: the mean age of patients with larynx cancer was 62 years and of control subjects 63 years. Of the total sample, over 95% were men, and over 90% were smokers. The presence of null genotypes for GTM1 was 50% in patients with larynx cancer (p = 0.042), while GSTT1 was 88.75% (p = 0.002). CYP1A1 rs4646903 T>C polymorphisms were detected in 100% of cases of larynx cancer and 17.39% of healthy subjects (p > 0.001). Conclusions: patients with larynx cancer present more gene GSTM1 and GSTT1 null polymorphisms, and CYP1A1 rs4646903 T>C polymorphisms.

Genetic Polymorphisms of Glutathione S-Transferase and Risk of Acute Myeloid Leukemia: Case-Control Study and Meta-Analysis

Background: Acute myeloid leukemia (AML) is a complex disease that is linked to genetic and environmental factors. The gluthatione S-transferase (GST) is a family of enzymes that play a crucial role in the detoxification of carcinogens. These compounds could cause DNA damage, which might lead to the development of cancer. Interindividual inherited differences caused by the presence of single nucleotide polymorphisms (SNPs) in detoxification enzyme, could play a major role in cancer predisposition. The present study aimed to investigate the association between GST gene polymorphisms and AML risk. Methods: The GSTP1 genotype was determined by the PCR-RFLP and multiplex PCR for GSTT1 and GSTM1. Meta-analysis was conducted to evaluate the association between GST gene and the risk of AML. Results: We found that GSTT1 null genotype was significantly associated with the risk of AML. However, GSTM1 and GSTP1 polymorphisms did not influence the AML risk. Subjects carrying the GSTM1 Present, GSTT1 null and GSTP1 Ile / Val et Val /Val genotypes had a higher risk of developing AML. The results of meta-analysis showed a positive association between GSTM1 null, GSTT1 null and Ile105Val GSTP1 polymorphisms and AML risk in East Asians, Caucasians, and mixed populations, respectively. Conclusion: GST gene polymorphisms may be risk factors for acute myeloid leukemia.

Environmental exposure pathway analysis of trace elements and autism risk in Pakistani children population

The pursuit of industrialization and urbanization in developing countries disrupt the fragile environment, resulting in biogeochemical extra-emission of the trace elements into human inhabitance causing serious health concerns. We aimed to determine the associations between Autism spectrum disorder (ASD) risk and exposure to trace elements (As, Zn, Ni, Pb, Hg, Cu, Cd, and Co), associations between the internal doses and environmental sources of these elements were also assessed. Genetic susceptibility to toxins was assessed through GSTT1 and GSTM1 null polymorphism analysis. Our results showed that lower BMI in children was significantly associated with ASD (p < 0.05, AOR = 0.86; 95% CI: 0.76, 0.98). As was significantly higher in both hair (p < 0.01, AOR = 18.29; 95% CI: 1.98, 169) and urine (p < 0.01, AOR = 1.04; 95% CI: 1.01, 1.06) samples from children with ASD; urinary Hg (p < 0.05, AOR = 2.90; 95% CI: 1.39, 6.07) and Pb (p < 0.05, AOR = 1.95; 95% CI: 1.01, 3.77) were also positively associated with ASD. Regarding the genetic susceptibility, Cu was significantly associated with GSTM1 positive genotype (p < 0.05, AOR = 1.05; 95% CI: 1.00, 1.10). Children inhabiting the urban areas exposed to significantly higher levels of studied trace elements. The Estimated Daily Intake (EDI) values highlighted that the different land use settings resulted in children's source specific exposure to studied trace elements. The exposure pathway analysis showed that the distal factors of land-use settings associated with children increased exposure risk for most of the investigated elements, noticeably As, Pb and Hg associated with ASD prevalence.

Association of maternal xenobiotic-metabolizing gene polymorphisms with risk of fetal growth restriction.

Aim: We investigated the association of maternal CYP1A1 MspI, CYP1A1 Ile462Val, GSTT1 null, GSTM1 null and NQO1 Pro187Ser polymorphisms with fetal growth restriction risk. Methods: The polymorphisms were genotyped on 1842 mothers (N=921 with fetal growth restriction and N=921 controls). Odds ratios were calculated to estimate the risk. Results: None of the five polymorphisms were associated with risk of fetal growth restriction among never-smoker mothers. However, the variant genotypes of CYP1A1 MspI and GSTM1 null polymorphisms were associated with an increased risk of fetal growth restriction among mothers who were either passive or active smokers. Conclusion:CYP1A1 MspI and GSTM1 null polymorphisms may interact with cigarette smoking to result in an increased risk of fetal growth restriction.

Age- and gender-independent association of glutathione S-transferase null polymorphisms with chronic myeloid leukemia.

The glutathione S-transferase (GST) genes encode enzymes that mediate the detoxification of xenobiotics by catalyzing the conjugation of glutathione (GSH) to xenobiotic substrates. The aim of the current study is to investigate the association between GSTT1 and GSTM1 polymorphisms and chronic myeloid leukemia (CML) among Sudanese patients. Patients with CML (n = 115) were recruited to the study from the Radiation and Isotope Centre Khartoum (RICK)-Sudan. Healthy individuals (n = 104) were included as controls. Genotyping of GSTT1 and GSTM1 polymorphisms was performed using multiplex PCR. Null deletions in the GSTT1 and GSTM1 genes are common in the Sudanese population (control group), with frequencies of 33.9% and 38.2%, respectively. The frequencies of GSTT1 (OR: 3.25, 95% CI: 1.87-5.65, p < 0.001) and GSTM1 (OR: 2.14, 95% CI: 1.25-3.67, p < 0.005) null genotypes were significantly higher in CML patients vs. controls. The distribution of GSTT1 and GSTM1 null polymorphisms was not different between male and female (p > 0.01) and young and old CML patients (p > 0.05). Hematological parameters were not affected by null polymorphisms in the patient group (p > 0.05). In addition, the frequency of GSTM1 null polymorphism was lower in advanced-phase CML patients compared to chronic-phase patients (p < 0.05). The GSTT1 and GSTM1 null polymorphisms are associated with CML among Sudanese patients, independently of their age and gender.

The GSTM1 and GSTT1 Null Genotypes Increase the Risk for Type 2 Diabetes Mellitus and the Subsequent Development of Diabetic Complications: A Meta-analysis.

Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study. Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted. Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism. Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.