Loci associated with genomic damage levels in chronic kidney disease patients and controls
Por:
Corredor, Z, da Silva, MI, Rodriguez-Ribera, L, Catalano, C, Hemminki, K, Coll, E, Silva, I, Diaz, JM, Ballarin, JA, Henandez, A, Forsti, A, Marcos, R, Pastor, S
Publicada:
1 abr 2020
Resumen:
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; GST01, 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; GL01, 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.
Filiaciones:
Corredor, Z:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Grp Mutagenesi, Edifici C, Bellaterra, Cerdanyola Del, Spain
da Silva, MI:
German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany
Rodriguez-Ribera, L:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Grp Mutagenesi, Edifici C, Bellaterra, Cerdanyola Del, Spain
Catalano, C:
German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany
Hemminki, K:
German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany
Lund Univ, Ctr Primary Hlth Care Res, Clin Res Ctr, Malmo, Sweden
Coll, E:
Fundacio Puigvert, Nephol Dept, Barcelona, Spain
Silva, I:
Fundacio Puigvert, Nephol Dept, Barcelona, Spain
Diaz, JM:
Fundacio Puigvert, Nephol Dept, Barcelona, Spain
Ballarin, JA:
Fundacio Puigvert, Nephol Dept, Barcelona, Spain
Henandez, A:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Grp Mutagenesi, Edifici C, Bellaterra, Cerdanyola Del, Spain
Carlos III Inst Hlth, Consortium Biomed Res Epidemiol & Publ Hlth CIBER, Madrid, Spain
Forsti, A:
German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany
Lund Univ, Ctr Primary Hlth Care Res, Clin Res Ctr, Malmo, Sweden
Marcos, R:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Grp Mutagenesi, Edifici C, Bellaterra, Cerdanyola Del, Spain
Carlos III Inst Hlth, Consortium Biomed Res Epidemiol & Publ Hlth CIBER, Madrid, Spain
Pastor, S:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Grp Mutagenesi, Edifici C, Bellaterra, Cerdanyola Del, Spain
Carlos III Inst Hlth, Consortium Biomed Res Epidemiol & Publ Hlth CIBER, Madrid, Spain
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