hOGG1 Ser326Cys and XRCC1 Arg399Gln polymorphisms associated with chronic obstructive pulmonary disease

Abstract

Background: Cigarette-smoke induced DNA damage can cause airway cell apoptosis and death, which may be associated with the development of chronic obstructive pulmonary disease (COPD). However, only 20% - 30% of smokers develop COPD, suggesting that different degrees of DNA repair produce different outcomes in smokers, i.e., part of them develop COPD. We investigated the association between polymorphisms in DNA repair genes hOGG1 (Ser326Cys) and XRCC1 (Arg399Gln), alone or in combination, and susceptibility of COPD.

Methods: Altogether 201 COPD patients and 309 controls were recruited and frequency-matched on age and sex. hOGG1 and XRCC1 genotypes were determined by PCR-restriction fragment length polymorphism analysis.

Results: The risk of COPD was not significantly different among individuals with Ser/Cys and Cys/Cys genotypes compared with those with hOGG1 Ser/Ser genotype. The risk of COPD was not significantly different among individuals with Gln/Gln genotype compared with those with XRCC1 Arg/Arg genotype, but it was significantly elevated among individuals with Arg/Gln genotype (adjusted odds ratios (OR) = 1.55, 95% confidence intervals (CI) 1.05 - 2.29, P = 0.029). Assessment of smoking status in current smokers compared with those with hOGG1 Ser/Ser genotype revealed that the risk of COPD was significantly elevated among individuals with Cys/Cys genotype (adjusted OR = 5.07, 95% CI 1.84 - 13.95, P = 0.002). Compared with those with XRCC1 Arg/Arg genotype, the risk of COPD was significantly elevated among individuals with Arg/Gln genotype (adjusted OR = 2.77, 95% CI 1.52 - 5.07, P = 0.001). Assessment of smoking exposure in light smokers compared with those with hOGG1 Ser/Ser genotype showed that the risk of COPD was significantly elevated among individuals with Cys/Cys genotype (adjusted OR = 4.02, 95% CI 1.05 - 16.80, P = 0.042). Compared with those with XRCC1 Arg/Arg genotype, the risk of COPD was significantly elevated among individuals with Gln/Gln genotype (adjusted OR = 4.48, 95% CI 1.35 - 14.90, P = 0.014). In heavy smokers compared with those with XRCC1 Arg/Arg genotype, the risk of COPD was significantly elevated among individuals with Arg/Gln genotype (adjusted OR = 2.55, 95% CI 1.42 - 4.58, P = 0.002). When hOGG1 Ser326Cys and XRCC1 Arg399Gln polymorphisms were evaluated together, compared with those with 0 - 1 of hOGG1 326Cys and XRCC1 399Gln alleles, the risk of COPD was significantly elevated among individuals with 3 - 4 of hOGG1 326Cys and XRCC1 399Gln alleles (adjusted OR = 3.18, 95% CI 1.86 - 5.43, P = 0.000). Assessment of smoking status and smoking exposure in current/light/heavy smokers showed that the risk of COPD was significantly elevated among individuals with 3 - 4 of hOGG1 326Cys and XRCC1 399Gln alleles (adjusted OR = 8.32, 95% CI 3.59 - 19.27, P = 0.000; OR = 5.46, 95% CI 2.06 - 14.42, P = 0.001; OR = 2.93, 95% CI 1.43 - 6.02, P = 0.003; respectively).

Conclusions: hOGG1 Ser326Cys and XRCC1 Arg399Gln polymorphisms are associated with the susceptibility to COPD. The risk of COPD is significantly elevated among current/light smokers with hOGG1 326Cys and XRCC1 399Gln.