Loci associated with genomic damage levels in chronic kidney disease patients and controls
(2020) In Mutation Research - Genetic Toxicology and Environmental Mutagenesis 852.- 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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2020-04
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- CKD patients, Genomic damage, Single nucleotide polymorphisms
- in
- Mutation Research - Genetic Toxicology and Environmental Mutagenesis
- volume
- 852
- article number
- 503167
- publisher
- Elsevier
- external identifiers
-
- scopus:85081651333
- pmid:32265040
- ISSN
- 1383-5718
- DOI
- 10.1016/j.mrgentox.2020.503167
- language
- English
- LU publication?
- yes
- id
- 8625e4b3-5b86-42c9-a8ed-1d2f56000208
- date added to LUP
- 2020-03-30 17:07:36
- date last changed
- 2024-04-03 04:29:59
@article{8625e4b3-5b86-42c9-a8ed-1d2f56000208,
abstract = {{<p>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.</p>}},
author = {{Corredor, Zuray and da Silva Filho, Miguel Inácio and Rodríguez-Ribera, Lara and Catalano, Calogerina and Hemminki, Kari and Coll, Elisabeth and Silva, Irene and Diaz, Juan Manuel and Ballarin, José Aurelio and Henández, Alba and Försti, Asta and Marcos, Ricard and Pastor, Susana}},
issn = {{1383-5718}},
keywords = {{CKD patients; Genomic damage; Single nucleotide polymorphisms}},
language = {{eng}},
publisher = {{Elsevier}},
series = {{Mutation Research - Genetic Toxicology and Environmental Mutagenesis}},
title = {{Loci associated with genomic damage levels in chronic kidney disease patients and controls}},
url = {{http://dx.doi.org/10.1016/j.mrgentox.2020.503167}},
doi = {{10.1016/j.mrgentox.2020.503167}},
volume = {{852}},
year = {{2020}},
}