Studies have been published recently regarding the association of oxidative stress and hypertension, and there is interest in the prevention and treatment of hypertension through reduction of oxidative stress. Epidemiological studies suggest that genetic polymorphism leads to different risks for disease despite exposure to the same environmental factors. Glutathione S-transferase (GST) forms a multigene family of phase II detoxification enzymes that are involved in the detoxification of xenobiotics by conjugating substances with glutathione. It has been reported that susceptibility to inflammation and the risk for cancers are increased in participants with GST mutant genotype.
This study was intended to investigate the association between hypertension and oxidative stress-related parameters and to assess these parameters in subclinical hypertensive patients using glutathione S-transferase polymorphisms. Also it examined whether daily supplementation with antioxidant food could modulate the antioxidant status and whether this modulation could be affected by GSTM1 and GSTT1 polymorphisms.
The first study was a cross-sectional observation study with a population of 227 hypertensive patients and 130 normotensive healthy subjects as controls. It was designed to compare the level of antioxidant status and the degree of lymphocyte DNA damage in the two groups and to evaluate the association of oxidative stress and hypertension. And then, assessed the antioxidant status and the degree of DNA damage in subclinical hypertensive patients in Korea regarding to glutathione S-transferase polymorphisms.
The second study evaluated the impact of GST polymorphisms on oxidative DNA damage and on the effectiveness of antioxidants in preventing this damage in human lymphocytes in vitro and ex vivo and identified subject materials to be used for human intervention study.
The third study evaluated the genetic susceptibility of nutritional intervention and suggested a gene tailored nutrition therapy by measuring the diminishing effect of oxidative stress-related parameters after nutrition intervention trials using antioxidants in 84 subclinical hypertensive patients with different GSTM1 and GSTT1 polymorphisms.
In the first study, the plasma levels of α-tocopherol, β-carotene, TRAP, and activity of GSH-Px were significantly lower in subclinical hypertensive patients than in normotensive subjects, while the levels of DNA damage, lipid peroxidation, triglyceride, total cholesterol, and LDL-cholesterol were increased in subclinical hypertensive patients. In subclinical hypertensive patients, GSTM1 mutant genotype or GSTM1/GSTT1 double mutant genotype were at increased risk of hypertension. The plasma levels of α-tocopherol increased significantly in GSTT1 wild genotype and the plasma levels of β-carotene increased significantly in the GSTT1 mutant genotype. DNA damage was significantly higher in the GSTM1 mutant genotype than in the wild genotype.
In the second study, the first selected juices that showed a high antioxidant activity were blueberry, grape, haruyachae purple, orange, and kale. Kale juice had significantly higher antioxidant activity than orange and haruyachae purple in the GSTM1 wild / GSTT1 mutant genotype.
In the third study, lymphocyte DNA damage was more decreased significantly and plasma vitamin C was increased in the GSTM1 mutant genotype, while decreased blood glucose was observed in the GSTM1 wild genotype. On the other hand, in case of GSTT1, there was a significant decrease in blood pressure and LDL-C and increase in plasma CD and HLD-C in the GSTT1 wild genotype, while decreased blood glucose was observed in the GSTT1 mutant genotype.
These results confirm that there are evident associations between blood pressure and oxidative stress-related parameters and between GSTM1 mutant genotype and risk of hypertension and suggest that the pathogenic role of oxidative stress in hypertension might be significant and that the GSTM1 mutant genotype is at higher risk of oxidative stress than the wild genotype. Our findings suggest that supplementation of kale juice affects blood pressure, blood glucose, antioxidant status, and lipid profiles in subclinical hypertensive patients depending on their GST genetic polymorphisms and the effect of kale juice is greater in the GSTM1 mutant and GSTT1 wild genotypes. This study may be helpful for the education of students for the demanding areas of tailored nutritional therapy, clinical nutrition, and genomics.