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Lack of association between glutathione peroxidase1 (GPx1) activity, Pro198Leu polymorphism and stenosis of coronary arteries: A population-based prediction.

ABSTRACT: BACKGROUND:We studied the association between erythrocyte glutathione peroxidase1 (GPx1) activity and rs1050450 (Pro198Leu) site with the stenosis of coronary arteries and, evaluated the Pro/Leu position within the predicted tertiary structure. METHODS:Subjects were recruited from who underwent coronary angiography (controls; n = 55, Stenosis < 5% and Patients; n = 95, Stenosis ? 50%). The GPx1 activity and rs1050450 C/T variants were determined using enzyme assay and RFLP-PCR techniques, respectively. The conserved regions and GPx1 tertiary structure were predicted using bioinformatics tools. RESULTS:We did not find significant association between GPx1 activity (P = 0.96), rs1050450 genotype distribution and coronary artery disease (adjusted OR = 0.79; 95%CI 0.28-2.2, P = 0.6). The polymorphic variants were not located at the predicted structural and functional domains so that it had not the significant role on the GPx1stability and function. CONCLUSIONS:In agreement with the results predicted from bioinformatics tools, we suggested that the GPx1 activity and rs1050450 (Pro198Leu) site are not involved in the development of stenosis of coronary arteries in the study population.

SUBMITTER: Najafi M

PROVIDER: S-EPMC4287826 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Lack of association between glutathione peroxidase1 (GPx1) activity, Pro198Leu polymorphism and stenosis of coronary arteries: A population-based prediction.

Najafi Mohammad M Ghasemi Hassan H Roustazadeh Abazar A Farajollahi Mohammad M

Meta gene 20141010

<h4>Background</h4>We studied the association between erythrocyte glutathione peroxidase1 (GPx1) activity and rs1050450 (Pro198Leu) site with the stenosis of coronary arteries and, evaluated the Pro/Leu position within the predicted tertiary structure.<h4>Methods</h4>Subjects were recruited from who underwent coronary angiography (controls; n = 55, Stenosis < 5% and Patients; n = 95, Stenosis ≥ 50%). The GPx1 activity and rs1050450 C/T variants were determined using enzyme assay and RFLP-PCR tec ...[more]

PMID: 25606455

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Project description:Since targeting oxidative stress markers has been recently recognized as a novel therapeutic target in cancer, it is interesting to investigate whether genetic susceptibility may modify oxidative stress response in cancer. The aim of this study was to elucidate whether genetic polymorphism in the antioxidant enzymes is associated with lipid peroxidation in breast cancer.We conducted a study among Polish women, including 136 breast cancer cases and 183 healthy controls. The analysis included genetic polymorphisms in five redox related genes: GPX1 (rs1050450), GPX4 (rs713041), SOD2 (rs4880), SEPP1 (rs3877899) and SEP15 (rs5859), lipid peroxidation, the activities of antioxidant enzymes determined in blood compartments as well as plasma concentration of selenium - an antioxidant trace element involved in cancer. Genotyping was performed using the Real Time PCR. Lipid peroxidation was expressed as plasma concentration of thiobarbituric acid reactive substances (TBARS) and measured with the spectrofluorometric method. Glutathione peroxidase activity was spectrophotometrically determined in erythrocytes (GPx1) and plasma (GPx3) by the use of Paglia and Valentine method. Spectrophotometric methods were employed to measure activity of cytosolic superoxide dismutase (SOD1) in erythrocytes (Beauchamp and Fridovich method) and ceruloplasmin (Cp) in plasma (Sunderman and Nomoto method). Plasma selenium concentration was determined using graphite furnace atomic absorption spectrophotometry.Breast cancer risk was significantly associated with GPX1 rs1050450 (Pro198Leu) polymorphism, showing a protective effect of variant (Leu) allele. As compared to the control subjects, lipid peroxidation and GPx1 activity were significantly higher in the breast cancer cases, whereas ceruloplasmin activity was decreased. After genotype stratification, both GPx1 activity and TBARS concentration were the highest in GPX1 Pro/Pro homozygotes affected by breast cancer. At the same time, there was a significant correlation between the level of lipid peroxidation and GPx1 activity among the cancer subjects possessing GPX1 Pro/Pro genotype (r?=?0.3043; p?=?0.0089), whereas such a correlation was completely absent in the cases carrying at least one GPX1 Leu allele as well as in the controls (regardless of GPX1 genotype).GPX1 polymorphism may be an important factor modifying oxidative stress response in breast cancer subjects. Further studies are needed to elucidate its potential clinical significance.

Project description:AimEvidence indicates there are still conflicts regarding CETP Taq1B polymorphism and coronary artery disease risk factors. Current findings about whether dietary patterns can change the relationship of the Taq1B on lipid profile and the severity of coronary arteries stenosis appears to be limited. The present research made an attempt to investigate this possible relationship.MethodsThis cross-sectional study involved 453 male and female participants with a mean age of 57 years. A validated 178-item food frequency questionnaire (FFQ) was used to assess dietary usual intake. Dietary patterns were extracted through principal component analysis (PCA). Taq1B variant was genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Two-way ANOVA was used to test the interaction between Taq1B polymorphism and dietary patterns.ResultsTwo dietary patterns were detected: the western dietary pattern (WDP) and the traditional dietary pattern (TDP). The frequency of Taq1B genotypes turned out to be 10.4, 72.4, and 17.2% for B1B1, B1B2, and B2B2, respectively. A significant difference was observed in TG and TG/HDL-C levels among TaqIB genotypes in higher adherence to TDP (P = 0.01 and P = 0.03, respectively). Taq1B showed a significant interaction with TDP for modulating TG levels and TG/HDL-C ratio (P = 0.02 and P = 0.04, respectively). Greater compliance to WDP demonstrated a significant difference in TG and TG/HDL-C levels across rs708272 genotypes (P = 0.03) after adjusting for confounding factors. Other lipid components and coronary arteries stenosis scores failed to show any relationship or significant difference across Taq1B genotypes or dietary patterns.ConclusionAdherence to TDP may adjust the association between the Taq1B variant and TG and TG/HDL-C levels in patients undergoing coronary angiography. To better understand the relationships, we suggest prospective studies in different race groups with multivariate approaches.

Dataset Information

Lack of association between glutathione peroxidase1 (GPx1) activity, Pro198Leu polymorphism and stenosis of coronary arteries: A population-based prediction.

Publications

Lack of association between glutathione peroxidase1 (GPx1) activity, Pro198Leu polymorphism and stenosis of coronary arteries: A population-based prediction.

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