Evaluation of DNA damage in COPD patients and its correlation with polymorphisms in repair genes.
BACKGROUND
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
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. andreag@unisc.br.
Andréa Lúcia Gonçalves
AL
da Silva
Helen Tais
HT
da Rosa
Thaís Evelyn
TE
Karnopp
Clara Forrer
CF
Charlier
Joel Henrique
JH
Ellwanger
Dinara Jaqueline
DJ
Moura
Lia Gonçalves
LG
Possuelo
Andréia Rosane de Moura
AR
Valim
Temenouga Nikolova
TN
Guecheva
João Antonio Pêgas
JA
Henriques
D000368:Aged; D000483:Alleles; D020552:Comet Assay; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008741:Methyl Methanesulfonate / Q000737:chemistry; D008875:Middle Aged; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000473:pathology; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; C101467:XRCC4 protein, human; D008741:Methyl Methanesulfonate; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human