Loci associated with genomic damage levels in chronic kidney disease patients and controls

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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.

Detaljer

Författare
  • Zuray Corredor
  • Miguel Inácio da Silva Filho
  • Lara Rodríguez-Ribera
  • Calogerina Catalano
  • Kari Hemminki
  • Elisabeth Coll
  • Irene Silva
  • Juan Manuel Diaz
  • José Aurelio Ballarin
  • Alba Henández
  • Asta Försti
  • Ricard Marcos
  • Susana Pastor
Enheter & grupper
Externa organisationer
  • Autonomous University of Barcelona
  • German Cancer Research Centre
  • Center for Primary Health Care Research
  • Fundació Puigvert
  • Carlos III Health Institute
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinsk genetik

Nyckelord

Originalspråkengelska
Artikelnummer503167
TidskriftMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volym852
StatusPublished - 2020 apr
PublikationskategoriForskning
Peer review utfördJa