Extracellular superoxide dismutase (EC-SOD) as a protective factor for risk of chronic obstructive pulmonary disease

Abstract

Tobacco smoke contains a high concentration of oxidants and is the primary cause of chronic obstructive pulmonary disease (COPD). Extracellular superoxide dismutase (EC-SOD) is the major antioxidant enzyme in the extracellular space of the lung and is part of the lung defense against these oxidants. We hypothesized that EC-SOD is a risk factor for COPD. We found that EC-SOD plasma levels were significantly higher (p<0.001) in 337 patients with COPD (147±7 ng·ml–1) versus 343 controls (96±9 ng·ml–1) and that lower FEV1s were associated with lower EC-SOD levels. To identify whether the EC-SOD gene was associated with COPD, we resequenced a subset of 188 subjects and identified 33 novel SNPs. Two of these SNPs (rs8192287 and rs8192288) were associated with a reduced odds of having COPD (OR 0.05 and 0.34; P<0.05). Haplotype analysis using a total of 5 EC-SOD SNPs (Table 1) further identified a protective haplotype (TTCGC) that was found in 11.4% of controls, but only 2.1% of subjects with COPD (P<0.001). These data indicate that EC-SOD genotype may partially predict whether smokers are resistant to the effects smoking.