Evaluation of DNA damage in COPD patients and its correlation with polymorphisms in repair genes
1 Santa Cruz Hospital and Department of Health and Physical Education, University of Santa Cruz do Sul - UNISC, Avenida Independência, 2293, Bloco 42, Bairro Universitário, Santa Cruz do Sul, RS, Brazil
2 Graduate Program in Cell and Molecular Biology, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil
3 Scientific Initiation of University of Santa Cruz do Sul - UNISC, Santa Cruz do Sul, RS, Brazil
4 Department of Biology and Pharmacy, University of Santa Cruz do Sul - UNISC, Santa Cruz do Sul, RS, Brazil
5 Laboratory of Genetic Toxicology, Federal University of Health Sciences of Porto Alegre - UFCSPA, Porto Alegre, RS, Brazil
6 Department of Biophysics, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil
7 Institute of Biotechnology, University of Caxias do Sul, Caxias do Sul, RS, Brazil
BMC Medical Genetics 2013, 14:93 doi:10.1186/1471-2350-14-93Published: 20 September 2013
We investigated a potential link between genetic polymorphisms in genes XRCC1 (Arg399Gln), OGG1 (Ser326Cys), XRCC3 (Thr241Met), and XRCC4 (Ile401Thr) with the level of DNA damage and repair, accessed by comet and micronucleus test, in 51 COPD patients and 51 controls.
Peripheral blood was used to perform the alkaline and neutral comet assay; and genetic polymorphisms by PCR/RFLP. To assess the susceptibility to exogenous DNA damage, the cells were treated with methyl methanesulphonate for 1-h or 3-h. After 3-h treatment the % residual damage was calculated assuming the value of 1-h treatment as 100%. The cytogenetic damage was evaluated by buccal micronucleus cytome assay (BMCyt).
COPD patients with the risk allele XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) showed higher DNA damage by comet assay. The residual damage was higher for COPD with risk allele in the four genes. In COPD patients was showed negative correlation between BMCyt (binucleated, nuclear bud, condensed chromatin and karyorrhexic cells) with pulmonary function and some variant genotypes.
Our results suggest a possible association between variant genotypes in XRCC1 (Arg399Gln), OGG1 (Ser326Cys), XRCC3 (Thr241Met), and XRCC4 (Ile401Thr), DNA damage and progression of COPD.