TY - JOUR
T1 - Levels of DNA damage (Micronuclei) in patients suffering from chronic kidney disease. Role of GST polymorphisms
AU - Pastor, Susana
AU - Rodríguez-Ribera, Lara
AU - Corredor, Zuray
AU - da Silva Filho, Miguel Inácio
AU - Hemminki, Kari
AU - Coll, Elisabeth
AU - Försti, Asta
AU - Marcos, Ricard
PY - 2018/12/1
Y1 - 2018/12/1
N2 - © 2018 Elsevier B.V. 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.
AB - © 2018 Elsevier B.V. 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.
KW - CKD patients
KW - GST polymorphisms
KW - Micronuclei
KW - Radiosensitivity
KW - Single nucleotide polymorphisms
U2 - 10.1016/j.mrgentox.2018.05.008
DO - 10.1016/j.mrgentox.2018.05.008
M3 - Article
C2 - 30389161
SN - 1383-5718
VL - 836
SP - 41
EP - 46
JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
ER -