Glutathione S-transferase P1 Polymorphisms Research Articles

Glutathione S-transferase M1, T1, and P1 polymorphisms and periodontitis in a Caucasian population: a case-control study

BackgroundGlutathione S-transferases (GSTs) play important roles in protecting cells against oxidative stress and toxic chemicals. This study aimed to investigate the distribution of GSTM1, GSTT1, and GSTP1 variants and their roles in periodontitis susceptibility in a Caucasian population.MethodsWe analyzed 406 participants, including 204 healthy controls and 203 periodontitis patients. A multiplex polymerase chain reaction (PCR) approach was used to analyze GSTM1 and GSTT1 loci. GSTP1 variants were detected by PCR-haplotyping method in a subgroup of participants (N = 350). Chi-square or Fisher´s exact tests were used to compare genotypic and allelic differences. The Bonferroni method was applied to correct for multiple comparisons (pcorr).ResultsThe GSTM1 genotype distribution did not differ significantly between controls and periodontitis patients (p = 0.44). Additionally, the wild/null genotypes of GSTT1, Ile105Val and Ala114Val frequencies of GSTP1 were not significantly different between the two groups after correction for multiple comparisons (p = 0.05, p = 0.55, p = 0.02, pcorr>0.05, respectively). The GSTM1 and GSTP1 Ile105Val gene variants were similarly distributed between non-smokers and smokers in both groups (p = 0.38, p = 0.20, and p = 0.14, p = 0.35, respectively). However, the wild genotype of the GSTT1 and Ala114Ala variant of the GSTP1 genes were present more frequently in non-smoking periodontitis patients than in non-smoking controls (p = 0.03, pcorr>0.05, and p = 0.009, pcorr>0.05, respectively) although their frequencies did not differ between smoking periodontitis patients and smoking controls (p = 0.23, p = 0.68, respectively).ConclusionsThis study in a Czech Caucasian population did not confirm a highly significant association between GST gene variants and susceptibility to periodontitis, as previously reported by Arshad and colleagues in Pakistanis. However, a weak relationship between GSTT1 and GSTP1 rs1138272 polymorphisms and periodontitis in non-smokers was observed.

GSTP1 rs4147581 C>G and NLRP3 rs3806265 T>C as Risk Factors for Chronic Obstructive Pulmonary Disease: A Case-Control Study.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory ailment influenced by a blend of genetic and environmental factors. Inflammatory response and an imbalance in oxidative-antioxidant mechanisms constitute the primary pathogenesis of COPD. Glutathione S-transferase P1(GSTP1) plays a pivotal role as an antioxidant enzyme in regulating oxidative-antioxidant responses in the pulmonary system. The activation of the NOD-like receptor thermal protein domain (NLRP3) inflammatory vesicle can trigger an inflammatory response. Several investigations have implicated GSTP1 and NLRP3 in the progression of COPD; nonetheless, there remains debate regarding this mechanism. Employing a case-control study design, 312 individuals diagnosed with COPD and 314 healthy controls were recruited from Gansu Province to evaluate the correlation between GSTP1 (rs4147581C>G and rs1695A>G) and NLRP3 (rs3806265T>C and rs10754558G>C) polymorphisms and the susceptibility to COPD. The presence of the GSTP1 rs4147581G allele substantially elevated the susceptibility to COPD (CGvs.CC:OR=3.11,95% CI=1.961-4.935, P<0.001;GGvs.CC:OR=2.065,95% CI=1.273-3.350, P=0.003; CG+GGvs.CC:OR=2.594,95% CI=1.718-3.916, P<0.001). Similarly, the NLRP3rs3806265T allele significantly increased the susceptibility to COPD (TC:TT:OR=0.432,95% CI=0.296-0.630; TC+CCvs.TT:OR=2.132,95% CI=1.479-3.074, P<0.001). However, no statistically significant association was discerned between the rs1695A>G and rs10754558G>C polymorphisms and COPD susceptibility (P>0.05). In summary, this study ascertained that the GSTP1 rs4147581C>G polymorphism is associated with increased COPD susceptibility, with the G allele elevating the risk of COPD. Similarly, the NLRP3 rs3806265T>C polymorphism is linked to elevated COPD susceptibility, with the T allele heightening the risk of COPD.

Polymorphism of glutathione S-transferase P1 of dogs with mammary tumours.

Mammary tumours constitute more than half of neoplasms in female dogs from different countries. Genome sequences are associated with cancer susceptibility but there is little information available about genetic polymorphisms of glutathione S-transferase P1 (GSTP1) in canine cancers. The aim of this study was to find single nucleotide polymorphisms (SNPs) in GSTP1 of dogs (Canis lupus familiaris) with mammary tumours compared to healthy dogs and to determine the association between GSTP1 polymorphisms and the occurrence of these tumours. The study population included 36 client-owned female dogs with mammary tumours and 12 healthy female dogs, with no previous diagnosis of cancer. DNA was extracted from blood and amplified by PCR assay. PCR-products were sequenced by Sanger method and analysed manually. The 33 polymorphisms were found in GSTP1: 1 coding SNP (exon 4), 24 non-coding SNPs (9 in exon 1), 7 deletions and 1 insertion. The 17 polymorphisms have been found in introns 1, 4, 5 and 6. The dogs with mammary tumours have significant difference from healthy in SNPs I4 c.1018 + 123 T > C (OR 13.412, 95%CI 1.574-114.267, P= .001), I5 c.1487 + 27 T > C (OR 10.737, 95%CI 1.260-91.477, P= .004), I5 c.1487 + 842 G > C (OR 4.714, 95% CI 1.086-20.472, P= .046) and I6 c.2481 + 50 A > G (OR 12.000, 95% CI 1.409-102.207, P= .002). SNP E5 c.1487 T > C and I5 c.1487 + 829 delG also differed significantly (P= .03) but not to the confidence interval. The study, for the first time, showed a positive association of SNPs in GSTP1 with mammary tumours of dogs, that can possibly be used to predict the occurrence of this pathology.

Association of GSTP1 and PLCE1 gene polymorphisms with primary esophageal cancer

To assess the association of polymorphisms of glutathione S-transferase P1 (GSTP1) and phospholipase C epsilon-1 (PLCE1) genes with the susceptibility of primary esophageal cancer and their interaction with environmental factors. 162 patients with primary esophageal cancer and 162 healthy controls were recruited in this cross-sectional study. Basic information such as gender, age, history of smoking and alcohol consumption and family history of esophageal cancer were collected. Single nucleotide polymorphisms at A105G locus of GSTP1 gene and rs3765524, rs2274223 and rs3781264 loci of PLCE1 gene were detected. A logistic regression model was established to analyze the risk factors of esophageal cancer and the interaction among the factors. The proportions of individuals with smoking history, family history of esophageal cancer and hot diet in esophageal cancer group were higher than those in the control group (P<0.05). Conditional Logistic regression analysis showed that smoking, family history of esophageal cancer and GG genotype at the rs2274223 locus of PLCE1 gene were the risk factors for esophageal cancer (P<0.05), and AG/GG genotypes at the A105G locus of GSTP1 gene were the protective factors for esophageal cancer (P<0.05). In the two-factor interaction model, both AA genotype at A105G locus of GSTP1 gene and GG genotype at rs2274223 locus of PLCE1 gene had an interaction with smoking, and the risk of esophageal cancer has increased by 83.6% and 85.7%, respectively (P<0.05). AA genotype at A105G locus of GSTP1 gene, GG genotype at rs2274223 locus of PLCE1 gene and smoking constituted the best three-factor interaction model, and the risk of esophageal cancer has increased by 244.0% (P<0.05). Four-factor interaction model analysis showed that the risk of esophageal cancer among individuals with AA genotype at A105G locus of GSTP1 gene, GG genotype at rs2274223 locus of PLCE1 gene, smoking and family history of esophageal cancer has increased by 264.4% (P<0.05). The AG and GG genotypes at the A105G locus of GSTP1 gene are protective factors for esophageal cancer, and the GG genotype at rs2274223 locus of PLCE1 gene is a risk factor, both of them may interact with smoking and affect the susceptibility to esophageal cancer.

The Relation of Haplotype ATP-binding Cassette B1 and Glutathione S-transferase P1 A313G Genes with Hematological Toxicity in Indonesian Breast Cancer Patients Receiving Chemotherapy.

ObjectivesHematological toxicity induced by chemotherapy is known to be caused by multiple factors, including genetic factors such as polymorphisms. The polymorphisms may occur in drug efflux transporter proteins and enzymes involved in drug metabolism. We investigate the incidence of hematological toxicities and their relation to the haplotype ATP-binding cassette B1 (ABCB1) which were polymorphisms of C1236T, C3435T, G2677T, and glutathione S-transferase P1 (GSTP1) A313G genes in Indonesian breast cancer patients who received anthracycline during chemotherapy.MethodsThis retrospective cohort study was conducted on 138 breast cancer patients who underwent three cycles of chemotherapy in H. Adam Malik Hospital, Medan, Indonesia, who satisfied the inclusion criteria. The DNA of these patients was extracted from the peripheral leukocytes. Single nucleotide polymorphism (SNP) ABCB1 and GSTP1 were examined by the polymerase chain reaction-restriction fragment length polymorphism method. Data on patient characteristics and the incidence of hematological toxicity after each of the three cycles of chemotherapy were obtained from the medical records. The variations in absolute neutrophil count (ANC) and anemia were analyzed using the Friedmann test and the Wilcoxon signed-rank test. The Kruskal-Wallis test was used to investigate the association of ABCB1 and GSTP1 polymorphisms with anemia and neutropenia. The frequency distributions of genotypes and alleles were determined using the Hardy-Weinberg Equilibrium (HWE).ResultsPost the chemotherapy cycles, there was decrease in ANC (Mean±SD: 5 644.4±2 962.5 mm3 vs. 3 034.8±2 049.6 mm3) and increase in anemia (12.1±1.5 g/dL vs. 11.2± 1.3 g/dL) (p < 0.050 for each). No relation was observed between ABCB1 polymorphism, either in each SNP or in the form of haplotype (the combination of more than one SNP), and the incidence of anemia and neutropenia (p > 0.050). There was also no correlation between GSTP1 polymorphisms, anemia and neutropenia incidence (p > 0.050). The ABCB1 and GSTP1 genotypes and alleles frequency distribution showed no deviation from HWE (p > 0.050).ConclusionsIndonesia breast cancer patients who underwent three cycles of chemotherapy demonstrated susceptibility to hematological toxicity by developing side effects such as anemia and neutropenia. However, no relationship was found between hematological toxicity and ABCB1 and GSTP1 polymorphisms.

The Association of Glutathione S-Transferase P1 Polymorphism to Imatinib Mesylate Resistance in Chronic Myelogenous Leukemia Patients According to Haematology Response at General Hospital Haji Adam Malik and Branch Hospital in Kota Medan

Objective: Variations in the genes coding for drug metabolism enzymes may explain the variability response to treatment. Previous studies reported that GSTP1 polymorphism was associated with the incidence of Imatinib Mesylate resistance as first-line therapy in CML patients. This study aims to determine the association between GSTP1 polymorphism and Imatinib Mesylate resistance in CML patients according to haematology response. Methods: Total of 46 people (consisting of 23 CML patients with Imatinib Mesilat resistance and 23 CML patients without Imatinib Mesilat resistance) at General Hospital H. Adam Malik and branch hospital in Medan City, Indonesia was analyzed in this study. Blood samples were taken for examination of GSTP1 polymorphism through Polymerase Chain Reaction (PCR). Resistance status was taken from medical records based on ELN criteria. Data were analyzed using Fisher's Exact test; p value &lt;0,05 was applied to each statistical test as significant. Result: The distribution of research subjects characteristic was divided into imatinib resistance and non-imatinib resistance groups. In both cases, the highest frequency was found in male (65,2% and 69,6%) in 35-44 years old group (34,8% and 39,1%). In the imatinib resistance group, the highest frequency was found in Javanese (39,1%) and GSTP1 polymorphism Ile/Ile (65,2%). In the non-imatinib-resistant group, the highest frequency was found in Batak tribe (43,5%) and GSTP1 polymorphism Ile/Val (52,2%). This study found 11 cases of leukocytosis and 7 cases of thrombocytosis in the imatinib resistance group. According to statistical measurement, p value was 0,142 (p&gt;0,05). Conclusion: The association of GSTP1 polymorphism to imatinib mesylate resistance in chronic myelogenous leukemia patients according to haematology response was not significant. Keywords: Chronic Myeloid Leukemia, GSTP1 Polymorphism, Imatinib Mesylate Resistance.

Individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on lung cancer risk: A meta-analysis and re-analysis of systematic meta-analyses.

Thirty-five previous meta-analyses have been reported on the individual glutathione S-transferase M1 (GSTM1) present/null, glutathione S-transferase T1 (GSTT1) present/null, and glutathione S-transferase P1 (GSTP1) IIe105Val polymorphisms with lung cancer (LC) risk. However, they did not appraise the credibility and explore the combined effects between the 3 genes and LC risk.We performed a meta-analysis and re-analysis of systematic previous meta-analyses to solve the above problems.Meta-analyses of Observational Studies in Epidemiology guidelines were used. Moreover, we employed false-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and the Venice criteria to verify the credibility of current and previous meta-analyses.Significantly increased LC risk was considered as “highly credible” or “positive” for GSTM1 null genotype in Japanese (odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.17–1.44, I2 = 0.0%, statistical power = 0.997, FPRP = 0.008, BFDP = 0.037, and Venice criteria: AAB), for GSTT1 null genotype in Asians (OR = 1.23, 95% CI = 1.12–1.36, I2 = 49.1%, statistical power = 1.000, FPRP = 0.051, BFDP = 0.771, and Venice criteria: ABB), especially Chinese populations (OR = 1.31, 95% CI = 1.16–1.49, I2 = 48.9%, Statistical power = 0.980, FPRP = 0.039, BFDP = 0.673, and Venice criteria: ABB), and for GSTP1 IIe105Val polymorphism in Asians (Val vs IIe: OR = 1.28, 95% CI = 1.17–1.42, I2 = 30.3%, statistical power = 0.999, FPRP = 0.003, BFDP = 0.183, and Venice criteria: ABB). Significantly increased lung adenocarcinoma (AC) risk was also considered as “highly credible” or “positive” in Asians for the GSTM1 (OR = 1.35, 95% CI = 1.22–1.48, I2 = 25.5%, statistical power = 0.988, FPRP < 0.001, BFDP < 0.001, and Venice criteria: ABB) and GSTT1 (OR = 1.36, 95% CI = 1.17–1.58, I2 = 30.2%, statistical power = 0.900, FPRP = 0.061, BFDP = 0.727, and Venice criteria: ABB) null genotype.This study indicates that GSTM1 null genotype is associated with increased LC risk in Japanese and lung AC risk in Asians; GSTT1 null genotype is associated with increased LC risk in Chinese, and GSTP1 IIe105Val polymorphism is associated with increased LC risk in Asians.

Pyrethroid exposure: as determinant of CYP1A1 and GSTP1 genetic variations in occupationally exposed Sindh farmers

Pyrethroid (PYR) is a class of pesticide which was frequently applied in agricultural fields of Sanghar in Pakistan. Consistent and over use of PYR may lead to health effects on workers who are occupationally exposed to pesticides every day. For assessment of PYR toxicity, Cytochrome-P450 (CYP1A1) and Glutathione–S-transferase P1 (GSTP1) code for xenobiotic metabolizing enzymes (XME) were investigated in Sanghar exposed studied population. To execute the case-control study, a total of 200 blood samples from PYR-exposed and control subjects were collected. Prior informed consent was taken from all the subjects. For determination of genetic variations, CYP1A1 (rs1048943) and GSTP1 (rs1695) regions were amplified using polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP). Resolved bands were visualized on 2 % agarose gel. Results indicated that in CYP1A1 polymorphism (rs1048943) there was no significant association between CYP1A1 genotypes AA, AG, GG and PYR toxicity (ϰ2= 2.03, p > 0.05) in exposed subjects. However, the impact of mutant allele G was further evaluated by genetic models, which demonstrated that G allele may show a risk for CYP1A1gene susceptibility to PYR exposure (OR: 8.608; CI: 1.056–70.172) p < 0.05 in dominant and in co-dominant model (OR:16.25; CI:1.94-135.84) p < 0.05 as well. In contrast, in GSTP1 (rs1695) polymorphism, a significant association was observed in genotypes AA, AG, GG (ϰ2= 8.03, p < 0.05) compared with control subjects. G allele may also exhibit a significant association with GSTP1 gene susceptibility and PYR-toxicity in co-dominant model (OR: 7.166; CI: 2.828–8.15) p < 0.001. This study may help to provide acquaintance about the pesticide hazardous effects.

Role of glutathione S-transferase P1 polymorphism in early transplant complications in patients undergoing allogeneic stem cell transplantation.

Complications in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) cause serious morbidity and mortality. Predicting patients at risk in advance and changing the symptomatic care and/or preparation regimen according to this risk assessment have been emphasized recently. Several single-nucleotide polymorphisms have been studied, and some were found to be responsible for early complications. Glutathione S-transferase P1 (GSTP1) is an enzyme involved in the detoxification process that reduces oxidative stress by reducing the number of free oxygen radicals. This study aimed to investigate the relationship between GSTP1 polymorphism and early complications of allo-HSCT, iron parameters, overall survival (OS), and transplantation-related mortality (TRM). A total of 50 patients diagnosed with acute myeloid leukemia (n = 23) or acute lymphoblastic leukemia (n = 27) who underwent allo-HSCT between May 2008 and February 2011 at Gazi University Faculty of Medicine, Stem Cell Transplantation Unit, were included. Of the 50 patients, 24 (48%) were women and 26 (52%) were men. The median age of the patients was 26 (16-74) years. GSTP1 polymorphism was detected in 23 (46%) patients, and 27 (54%) had no polymorphism (wild type). The two groups were compared in terms of early toxicity after transplantation, according to the preparation regimen. The group with GSTP1 polymorphism was found to have a high transferrin saturation index (P < 0.05). Patients with no GSTP1 polymorphism showed a high grade III-IV anemia ratio (P < 0.05). The presence of sinusoidal obstruction syndrome and graft-versus-host disease was similar in both groups (P > 0.05). OS and TRM were higher in the GSTP1 polymorphism group, but no statistical difference was found between the two groups (P > 0.05). TSI was higher in the GSTP1 polymorphism group. GSTP1 polymorphism had no effect on early transplantation complications. Although the OS and TRM ratios were higher in the GSTP1 polymorphism group, no statistically significant difference was found between the groups. Further studies with larger sample size are needed.

The morbidity and mortality of COVID-19 are correlated with the Ile105Val glutathione S-transferase P1 polymorphism

BackgroundOxidative stress is an important issue in coronavirus disease 2019 (COVID-19). Considering that glutathione S-transferase P1 (GSTP1) is involved in cellular detoxification, it may play an important role in susceptibility to infection with SARS-CoV-2 and/or its outcome. In the present study, the association between the Ile105Val GSTP1 polymorphism (rs1695) and susceptibility to SARS-CoV-2 infection, as well as its outcome was investigated. Data on the prevalence (per 106 people), case-fatality (per 100 infected cases), and mortality (per 106 people) of COVID-19 and various potential confounders (the life expectancy at birth, density of medical doctors, density of nursing and midwifery personnel, and the gross national income per capita) were used. The latest data available for 45 countries were used for the study.ResultsIn multivariate linear regression analyses, the Val105 allelic frequency showed positive association with the log-prevalence (partial r = 0.308, p = 0.042) and log-mortality of COVID-19 (partial r = 0.316, p = 0.037). The log-fatality did not show association with the allelic frequency. In the next step, only countries with the gross national income per capita more than $15,000 were included in the analysis. In the selected countries, the frequency of Val105 was positively associated with the log-prevalence (partial r = 0.456, p = 0.009) and log-mortality of COVID-19 (partial r = 0.544, p = 0.001).ConclusionsThe present findings indicate that countries with higher Val105 allelic frequency of the rs1695 polymorphism showed higher prevalence and mortality of COVID-19.

Glutathione S-Transferase P1 Polymorphism on Exon 6 and Risk of Hepatocellular Carcinoma in Thai Male Patients

Introduction: Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the fourth leading cause of cancer-related deaths worldwide. HCC cases are two to four times more common in males than in females, and the highest incidence is found in Asia and Sub-Saharan Africa. This gender disparity is the result of different behavioral risk factors, such as smoking and drinking alcohol. Glutathione S-Transferase P1 (GSTP1) is an enzyme that is involved in the detoxification of carcinogenic electrophiles. GSTP1 codon 105 in exon 5 and codon 114 in exon 6 polymorphisms result in decreased enzyme detoxification activity, which is the cause of many cancers. Objectives: This study aims to investigate the associations between GSTP1 polymorphism, HCC patients, and the risk factors for HCC. It is hoped that this research will provide useful knowledge on the effects of genetic GSTP1 polymorphism in Thai HCC patients. Methods: DNA from 44 Thai HCC patients and 52 healthy controls was analyzed for GSTP1 exon 5 and exon 6 polymorphisms by PCR-RFLP. The associations between GSTP1 polymorphism, the control group, and clinicopathological parameters were determined. Results:The results show that GSTP1 exon 6 polymorphism genotypes (C/T) were correlated with an increased risk of HCC susceptibility (OR = 4.40). Moreover, exon 6 polymorphism genotypes (C/T) were associated with the gender of patients (p = 0.015), but no relationships were found between GSTP1 exon 5 polymorphism and the clinicopathological data of patients. Conclusions: The results suggest that the GSTP1 exon 6 polymorphism genotype was associated with an increase in the risk of HCC in male patients and that it tended to be related to cancer differentiation. No association was found between GSTP1 exon 5 polymorphism and the risk of HCC.

The association between GSTP1 polymorphism and pre-eclampsia risk: a system review and meta-analysis.

Oxidative stress is thought to play an important role in the pathophysiology of pre-eclampsia. Polymorphism of Glutathione S-transferase P1 (GSTP1) protect cells against the cytotoxic effects of reactive compounds. Published data on the association between the GSTP1 polymorphism and pre-eclampsia risk are controversial. A meta-analysis was performed to assess whether the polymorphisms of GSTP1 are associated with pre-eclampsia risk. Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases were searched to identify eligible studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for GSTP1 polymorphism and pre-eclampsia were appropriately derived from fixed-effects or random effects models. A total of six studies were enrolled in this meta-analysis. The pooled analyses revealed that GSTP1 polymorphism was not associated with pre-eclampsia risk. Heterogeneity among studies was founded in allele contrast. Galbraith plot analyses were performed to assess the source of heterogeneity and one study was found to be contributor of heterogeneity. The heterogeneity decreased significantly after excluding that study. Present meta-analysis demonstrates that GSTP1 polymorphism may be not correlated with pre-eclampsia risk.

Association of Lipid Peroxidation/Antioxidant System Activity with Glutathione S-Transferase P1 Polymorphisms in Infertile Men

Association of Lipid Peroxidation/Antioxidant System Activity with Glutathione S-Transferase P1 Polymorphisms in Infertile Men

Associations of AHR, CYP1A1, EPHX1, and GSTP1 genetic polymorphisms with small-for-gestational-age infants

Objective To investigate the influences of aryl hydrocarbon (AHR), cytochrome P450 (CYP1A1), epoxide hydrolase 1 (EPHX1), and glutathione S-transferase P1 (GSTP1) genetic polymorphisms on small-for-gestational-age (SGA) infants. Methods This nested case-control study (126 cases and 381 controls) was based on a prospective cohort study in Shanxi Province, China. We collected the general information of subjects using questionnaire and identified their single nucleotide polymorphisms by the MassARRAY genotyping platform. Results The polymorphisms of CYP1A1 (rs4646421 and rs4646903) and EPHX1 (rs1051740) were significantly associated with SGA. Neonates of women with EPHX1 (rs1051740) and GSTP1 (rs1695) variant alleles were at a significantly increased risk of SGA compared with the reference group (OR = 5.26; 95% CI, 1.08–25.66), as were neonates of women with CYP1A1 (rs4646903) and EPHX1 (rs1051740) variant alleles (OR = 7.11; 95% CI, 1.55–32.62). The results of strata analysis by AHR (rs2282883 and rs17137566) showed that the associations between the polymorphisms of CYP1A1 (rs4646421 and rs4646903) EPHX1 (rs1051740), GSTP1 (rs1695) and SGA were of significance in women with variant heterozygous or homozygous genotype. Conclusions CYP1A1 (rs4646421 and rs4646903), EPHX1 (rs1051740), and GSTP1 (rs1695) genetic variances might increase the risk of SGA. AHR (rs2282883 and rs17137566) resulted in estimated effects varying across strata on CYP1A1 (rs4646421 and rs4646903), EPHX1 (rs1051740), and GSTP1 (rs1695).

Multiple logistic regression analysis predicts cancer risk among tobacco usage with glutathione S-transferase p1 genotyping in patients with head and neck cancer.

Numerous studies have been investigated to understand the association between glutathione S-transferase P1 (GSTP1) polymorphism and risk of head and neck cancer (HNC) but yielded contradictory results, and no studies could confirm polymorphism in GSTP1 and that tobacco usage increases the risk of HNCs. Therefore, this study aimed to understand the association of GSTP1 Ile105Val polymorphism with or without tobacco usage in carcinogenesis and clinicopathological characteristics of patients with HNC. Binary logistic regression analysis was performed to predict HNC risk with tobacco use and GSTP1 genotyping. Five predictor variables such as gender, age, tobacco usage, familial, and GSTP1 genotypes were included in the model. The results of the logistic regression analysis show that the full model which considered all the five independent variables together was statistically significant, log-likelihood = -111.820, and all slopes are zero: G = 74.297, degree of freedom (DF) = 5, P = 0.000. The strongest predictor in this model is tobacco usage (odds ratio = Z = -5.16, P = 0.000). The study concludes that multiple logistic regression analysis model could predict the risk factors in case-control studies where control samples are compromised.

Glutathione s-transferase m1, t1, and p1 gene polymorphism in exudative age-related macular degeneration: a preliminary report.

To elucidate whether the gene polymorphisms of glutathione S-transferase (GST) M1, T1, and P1 are associated with the development of exudative age-related macular degeneration. The authors genotyped 35 white patients with exudative age-related macular degeneration and 159 healthy controls. Genomic DNA from peripheral blood was examined using polymerase chain reaction and defined for the genetic polymorphisms of GST. No association was observed between GSTM1, GSTT1, and GSTP1 polymorphisms and age-related macular degeneration risk (p>0.05). The frequencies of the combination of the GSTM1 (null) and GSTP1 (mutant), GSTM1 (null), and GSTT1 (null) genotype polymorphisms in patients with exudative age-related macular degeneration differed greatly from those of the control group (p=0.001 OR [95% CI]: 7.70 [2.28-25.98] and p=0.007 OR [95% CI]: 3.88 [1.51-10.02], respectively). The present study suggests that the GSTM1 (null) and GSTT1 (null), GSTM1 (null), and GSTP1 (mutant) combinations may be a genetic risk factor for the development of exudative age-related macular degeneration. However, the potential role of GST polymorphisms as a marker of susceptibility to age-related macular degeneration needs further studies in a larger number of patients. (Eur J Ophthalmol 2006; 16: 105-10).

Association of glutathione S-transferase polymorphisms with the severity of mustard lung

Introduction: Glutathione S-transferase (GST) is one of the major detoxifiers in alveoli. Polymorphism in GST genes can influence the ability of individuals to suppress oxidative stress and inflammation. The present study was aimed to explore the hypothesis that the genetic polymorphisms of GST T1, M1 and P1 are associated with the severity of the mustard lung in the sulfur mustard-exposed individuals. Methods: Blood samples were taken from 185 sulfur mustard-exposed and 57 unexposed subjects. According to the stage of the mustard lung, sulfur mustard-exposed patients were categorized in the mild/moderate and severe/very severe groups. A multiplex PCR method was conducted to identify GSTM1 and GSTT1 null genotypes. To determine the polymorphisms of GSTP1 in exon 5 (Ile105Val) and exon 6 (Ala114Val), RFLP-PCR method was performed. Results: The frequency of GSTM1 homozygous deletion was significantly higher in the severe/very severe patients compared with the mild/moderate subjects (66.3% vs. 48%, P = 0.013). The GSTM1 null genotype was associated with the severity of mustard lung (adjusted odds ratio [OR], 2.257; 95% CI, 1.219-4.180). There was no significant association between GSTT1 and GSTP1 polymorphisms with the severity of the mustard lung. Conclusion: The different distribution of GSTM1 null genotype in severe/very severe and mild/moderate groups indicated that the severity of the mustard lung might be associated with the genetic polymorphism(s).

Oxidative stress markers and genetic polymorphisms of glutathione S-transferase T1, M1, and P1 in a subset of children with autism spectrum disorder in Lagos, Nigeria

The role of oxidative stress has been identified in the development of autism spectrum disorder (ASD), and polymorphisms of glutathione S-transferase have been associated with some diseases linked to oxidative stress. Hence, we evaluated the serum levels of oxidative stress markers and investigated genetic polymorphisms of glutathione S-transferase associated with autism. Forty-two children clinically diagnosed with ASD using the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria and a clinical interview were included in the study. Twenty-three age-matched controls without any known genetic/developmental disorder were also recruited. Oxidative stress markers along with the genetic polymorphisms of glutathione S-transferase were determined. Reduced glutathione in ASD patients was significantly lower than the control (P = 0.008), whereas other oxidative stress markers measured were not significantly different in both the control and case populations. The frequencies of GSTT1 and GSTM1 null genotypes were lower among the controls compared with the cases, however, no association risk was observed. The observed risk of carrying Val/Val genotype among the cases was approximately six times that of the controls. Individuals with ASD showed a significant diminished level of reduced glutathione, however, the distribution of GSTT1, GSTM1, and GSTP1 polymorphisms was not found to be associated with autism in this study population.

Genetic Polymorphisms of Cytochrome P4501A1 (CYP1A1) and Glutathione S-Transferase P1 (GSTP1) and Risk of Hepatocellular Carcinoma Among Chronic Hepatitis C Patients in Egypt.

Cytochrome P450 1A1 (CYP1A1) and Glutathione S-transferase P1 (GSTP1) genes are involved in the metabolism of many carcinogens. Polymorphisms in these genes with altered enzyme activity have been reported. The present study evaluated the synergistic effect between CYP1A1 and GSTP1 gene polymorphisms and smoking on development of HCV-related liver disease and hepatocellular carcinoma (HCC). The patients group comprised 40 patients with HCC and 40 patients with liver cirrhosis. The control group comprised 40 healthy subjects having no history of malignancy. The genetic polymorphisms were studied using polymerase chain reaction restriction fragment length polymorphism (PCR RFLP) technique on blood samples. The number of current or former smoker among HCC and cirrhotic patients as well as the median Pack/year of cigarette smoked were significantly higher in HCC and liver cirrhotic patients than in control group. Subjects with CYP1A1 gene variants (m1 and m3) had no significant risk to develop cirrhosis or HCC compared to control group. Individuals carrying the Ile/Val genotype of GSTP1 had a significant increased risk of HCC (OR of 2.2, 95% CI 1.143-4.261) and had larger tumor size. No significant risk was observed on combining both genes variants or on combining smoking with variants of both genes. In conclusion, the GSTP1 Ile/Val genotype and Val allele are associated with an increased risk of HCC. CYP1A1 and GSTP1 genes variants interaction did not increase the risk of HCC.

Associations Among Glutathione S-Transferase T1, M1, and P1 Polymorphisms and the Risk of Oral Leukoplakia.

The potential association between glutathione S-transferase (GST) M1, T1, P1 polymorphisms and the risk of oral leukoplakia (OLK) has been extensively studied. However, the results of previous studies have been contradictory. In an effort to resolve these different findings we performed a meta-analysis. Eligible articles were identified by a search of PubMed, the China National Knowledge Infrastructure (CNKI), MEDLINE, EMBASE, and the Web of Science databases through December 1, 2015. Crude odds ratios (ORs) with 95% confidence intervals were used to evaluate the risk of OLK by tobacco use, ethnicity, and OLK subtype. A total of 3122 cases and 6037 controls were included in the meta-analysis. The results indicated that the glutathione S-transferase Mu1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms increase the risk of OLK (OR = 1.838, 95% CI = 1.582-2.134 and OR = 1.337, 95% CI = 1.132-1.579, respectively), especially in the groups with tobacco use (OR = 2.478, 95% CI = 2.032-3.020 and OR = 2.034, 95% CI = 1.486-2.783, respectively). Conversely the glutathione S-transferase P1 (GSTP1) polymorphism did not demonstrate a significant relationship with OLK risk (OR = 1.139, 95% CI = 0.900-1.442). The GSTM1 and GSTT1 null polymorphisms were identified as being significantly associated with an increased risk of OLK within the German and Indian populations: German subgroup (GSTM1: OR = 11.555, 95% CI = 7.465-17.884), Indian subgroup (GSTM1: OR = 1.333, 95% CI = 1.084-1.638; GSTT1: OR = 1.332, 95% CI = 1.057-1.679). Our findings provide evidence that the GSTT1 and GSTM1 null polymorphisms may be risk factors of OLK, especially for persons who use tobacco, whereas the GSTP1 polymorphism does not contribute to the development of OLK. Thus, detection of GSTT1 and GSTM1 null polymorphisms may be promising biomarkers for the OLK susceptibility.