Levels of DNA damage (Micronuclei) in patients suffering from chronic kidney disease. Role of GST polymorphisms

Abstract

Chronic kidney disease (CKD) patients are characterized by the presence of high levels of DNA damage, and a poor response to ionizing radiation. In this study, we proposed that variants in GST genes could explain this fact. One-hundred twenty seven CKD patients and one-hundred forty five controls constituted the studied groups. Micronuclei (MN) frequency was determined in peripheral blood lymphocytes at both basal level, and after challenging the cells with 0.5 Gy of ionizing radiation. The following polymorphisms: GSTP1 (rs749174), GSTO1 (rs2164624), and GSTO2 (rs156697) were evaluated in the two groups. Results indicate that gene variants were distributed differentially between CKD patients and controls. Although GSTO1 and GSTO2 variants were associated with lower levels of MN, this was observed in both CKD patients and controls. When net MN values were determined after irradiation, GSTO1 and GSTO2 variants were also associated with lower MN-frequencies. On the contrary, individuals with the GSTP1 variant showed higher values of induced MN. In conclusion, we have demonstrate that the selected GST polymorphism play a role in the incidence of CKD, and affects the levels of MN. Interestingly, the modulating effects observed on both, the basal and induced levels of DNA damage, are characteristic of the overall population, not only of the CKD patients.