The common variant in the GSTM1 and GSTT1 genes is related to markers of oxidative stress and inflammation in patients with coronary artery disease: a case-only study.
ABSTRACT Recent studies suggest that the common variant in the GSTM1 and GSTT1 genes modifies the risk of coronary artery disease (CAD), however, it is unclear whether the risk of CAD modulated by variants in the GSTM1 and GSTT1 genes was associated with alterations of indices of oxidative stress and inflammation. Our study is an attempt to provide insight into the role of GST genetic variant and markers of oxidative stress and inflammation in CAD patients. A total of 719 Chinese CAD patients were successfully genotyped. Plasma total antioxidant status (TAOS), glutathione(GSH), C-reactive protein (CRP), fibrinogen (FIB) and white blood cell count (WBC) were determined to evaluate the oxidative stress and inflammatory response. The correlations between GSTM1/GSTT1 genotypes and alterations of indices of oxidative stress and inflammation were analyzed. We found GSTM1-0/GSTT1-0 subjects had higher CRP and FIB and lower TAOS compared to patients with wild-type GSTM1/GSTT1 genes. A stepwise elevations in age, the incidences of hypertension and diabetes mellitus, levels of FIB and the number of WBC were associated with increased number of stenosed vessels. Reductions of plasma TAOS and GSH were associated with increased number of stenosed vessels. Our results suggest that GST polymorphisms maybe modify the effect on markers of oxidative stress and inflammation in Chinese CAD patients.
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ABSTRACT: OBJECTIVE: To our knowledge, no data have yet shown the combined effects of GSTM1/GSTT1 gene polymorphisms with high consumption of a fruit and vegetable diet on the body's antioxidant capacity. A 2-wk dietary intervention in healthy participants was conducted to test the hypothesis that the antioxidant biomarkers in individuals with different glutathione-S-transferases (GST) genotypes will be different in response to a high fruit-juice and vegetable diet. METHODS: In our study, 24 healthy volunteers with different GST genotypes (12 GSTM1+/GSTT1+ and 12 GSTM1-/GSTT1- participants) consumed a controlled diet high in fruit-juice and vegetables for 2 wk. Blood and first-void urine specimens were obtained at baseline, 1-wk, and 2-wk intervals. The antioxidant capacity-related biomarkers in blood and urine were observed and recorded at the scheduled times. RESULTS: Erythrocyte GST and glutathione reductase (GR) activities response to a high fruit-juice and vegetable diet are GST genotype-dependent. Two weeks on the high fruit-juice and vegetable diet increased GST and GR activities in the GSTM1+/GSTT1+ group (P < 0.05 compared with baseline or GSTM1-/GSTT1- group), although no effects were observed on GST and GR activities in GSTM1-/GSTT1- participants. Dietary intervention increased total antioxidant capacity and decreased plasma malondialdehyde content in all participants (P < 0.05 compared with baseline), whereas GSTM1+/GSTT1+ participants respond more quickly to a high fruit-juice and vegetable diet than GSTM1-/GSTT1- participants. The diet intervention was effective in enhancing glutathione peroxidase and catalase activities in all participants (P < 0.05 compared with baseline), although there was no influence on erythrocyte superoxide dismutase activity (P > 0.05). CONCLUSION: The effects of a diet rich in fruit-juice and vegetables on antioxidant capacity were dependent on GSTM1/GSTT1 genotypes.Nutrition 02/2013; · 2.86 Impact Factor
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ABSTRACT: The prevalence, incidence and mortality of all cardiovascular disorders (CVD) are two- to eightfold higher in persons with diabetes than in those without diabetes. Predicting and understanding the causes of CVD still represents an enormous challenge for clinical and basic cardiovascular science. Similarly, the fundamental mechanism by which diabetic patients are more prone to heart failure is unclear and prevention of such cardiac risk remains a major challenge for which new strategies are needed. Imbalance between free radicals and anti-oxidant defenses is associated with cellular dysfunctions leading to the pathophysiology of various diseases. Evidence suggests that diabetes is associated with a reduced overall antioxidant defense system and the increased oxidative stress. This may contribute to the pathogenesis of the diabetic complications, notably the emergence of premature atherosclerosis. The transcription factor NF-E2-related factor 2/antioxidant response element (Nrf2/ARE) regulates the expression of many detoxifying genes such as catalase, superoxide dismutase, UDP-glucuronosyltransferase, c-glutamylcysteine synthetase, NAD(P)H quinone oxidoreductase 1, glutathione- S-transferase, glutathione peroxidase-1 and heme oxygenase-1. Polymorphic effects of these antioxidant genes and their regulatory regions have higher relevancy to the susceptibility to clinical conditions such as diabetes, obesity and cardiovascular diseases. Thus, the present review aims to explore the relationship between free radicals, diabetes and its associated complications with respect to the genetic makeup of Nrf2/ARE regulated genes in an effort to expand treatment options.Current Medicinal Chemistry 06/2013; · 3.72 Impact Factor