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- Corredor, Zuray, et al.
(author)
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Loci associated with genomic damage levels in chronic kidney disease patients and controls
- 2020
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In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis. - : Elsevier BV. - 1383-5718. ; 852
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Journal article (peer-reviewed)abstract
- Chronic kidney disease (CKD) is a multifactorial disorder with an important genetic component, and several studies have demonstrated potential associations with allelic variants. In addition, CKD patients are also characterized by high levels of genomic damage. Nevertheless, no studies have established relationships between DNA damage, or genomic instability present in CKD patients, and gene polymorphisms. To fill in this gap, the potential role of polymorphisms in genes involved in base excision repair (OGG1, rs1052133; MUTYH, rs3219489; XRCC1, rs25487), nucleotide excision repair (ERCC2/XPD, rs1799793, rs171140, rs13181; ERCC4, rs3136166); phase II metabolism (GSTP1, rs749174; GSTO1, rs2164624; GSTO2, rs156697), and antioxidant enzymes (SOD1, rs17880135, rs1041740, rs202446; SOD2, rs4880; CAT, rs1001179; GPX1, rs17080528; GPX3, rs870406: GPX4, rs713041) were inquired. In addition, some genes involved in CKD (AGT, rs5050; GLO1, rs386572987; SHROOM3, rs17319721) were also evaluated. The genomic damage, the genomic instability, and oxidative damage were evaluated by using the micronucleus and the comet assay in 589 donors (415 CKD patients and 174 controls). Our results showed significant associations between genomic damage and genes directly involved in DNA repair pathways (XRCC1, and ERCC2), and with genes encoding for antioxidant enzymes (SOD1 and GPX1). GSTO2, as a gene involved in phase II metabolism, and MUTYH showed also an association with genomic instability. Interestingly, the three genes associated with CKD (AGT, GLO1, and SHROOM3) showed associations with both the high levels of oxidatively damaged DNA and genomic instability. These results support our view that genomic instability can be considered a biomarker of the CKD status.
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| 2. |
- Pastor, Susana, et al.
(author)
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Levels of DNA damage (Micronuclei) in patients suffering from chronic kidney disease. Role of GST polymorphisms
- 2018
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In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis. - : Elsevier BV. - 1383-5718. ; 836, s. 41-46
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Journal article (peer-reviewed)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.
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