Lymphocyte DNA damage and plasma antioxidant status in Korean subclinical hypertensive patients by glutathione S-transferase polymorphism

Abstract

BACKGROUND/OBJECTIVESGlutathione S-transferase (GST) forms a multigene family of phase II detoxification enzymes which are involved in the detoxification of xenobiotics by conjugating substances with glutathione. The aim of this study is to assess the antioxidative status and the degree of DNA damage in the subclinical hypertensive patients in Korea using glutathione S-transferase polymorphisms.SUBJECTS/METHODSWe examined whether DNA damage and antioxidative status show a difference between GSTM1 or GSTT1 genotype in 227 newly diagnosed, untreated (systolic blood pressure (BP) ≥ 130 mmHg or diastolic BP ≥ 85 mmHg) subclinical hypertensive patients and 130 normotensive subjects (systolic BP < 120 mmHg and diastolic BP < 80 mmHg). From the blood of the subjects, the degree of the DNA damage in lymphocyte, the activities of erythrocyte superoxide dismutase, the catalase, and the glutathione peroxidase, the level of glutathione, plasma total radical-trapping antioxidant potential (TRAP), anti-oxidative vitamins, as well as plasma lipid profiles and conjugated diene (CD) were analyzed.RESULTSOf the 227 subjects studied, 68.3% were GSTM1 null genotype and 66.5% were GSTT1 null genotype. GSTM1 null genotype had an increased risk of hypertension (OR: 2.104, CI: 1.38-3.35), but no significant association in GSTT1 null genotype (OR 0.982, CI: 0.62-1.55). No difference in erythrocyte activities of superoxide dismutase, catalase, or glutathione peroxidase, and plasma TRAP, CD, lipid profiles, and GSH levels were observed between GSTM1 or GSTT1 genotype. Plasma levels of α-tocopherol increased significantly in GSTT1 wild genotype (P < 0.05); however, plasma level of β-carotene increased significantly in GSTT1 null genotype (P < 0.01). DNA damage assessed by the Comet assay was significantly higher in GSTM1 null genotype than wild genotype (P < 0.05).CONCLUSIONSThese results confirm the association between GSTM1 null genotype and risk of hypertension as they suggest that GSTM1 null genotype leads to an increased oxidative stress compared with wild genotype.

Genetic polymorphisms associated with reactive oxygen species and blood pressure regulation

“…The GSTA1*B allele is considered as a genetic risk factor for hypertension in Japanese 374 . The association between the GSTT1 null and hypertension was reported in Italian women but not men 198 and GSTM1 null genotype with hypertension in Korean men and women 199 . The GST P1b-1b genotype causes prolonged exposure to ROS and increased risk of pre-eclampsia 375 ; GSTP1 313A>G with preeclampsia in Maya-Mestizo women 201 .…”

Biotoxins Mediated DNA Damage and Role of Phytochemicals in DNA Protection

“…Because of constant exposure of the genome to various xenobiotics, the DNA gets damaged. This event can produce a variety of genetic disorders which might be inherited from one generation to the other [4,5] The DNA damaging potential of xenobiotics has been reported well by several workers. While the impact of biotoxins on DNA has been described by only a small number of workers, the results however, have been inconclusive.…”

Impact of AKT1 polymorphism on DNA damage, BTG2 expression, and risk of colorectal cancer development

“…Many genes sequence variations lead to the pathogenesis of inherited and sporadic forms of colorectal cancer. 2,3 AKT, also known as Protein Kinase B (PKB), is a serine/threonine protein kinase which was originally discovered as an oncogene transduced by the acute transforming retrovirus (PKB-8/AKT8), isolated from mouse leukemia. 4,5 AKT is the downstream target of PI3K signaling that triggers a number of biological processes including cell survival, cell growth, glucose metabolism, angiogenesis, cell cycle entry cell motility, and also stimulate malignant transformation of cells and tumor progression.…”