Genetically increased antioxidative protection and decreased chronic obstructive pulmonary disease

Am J Respir Crit Care Med. 2006 Apr 15;173(8):858-64. doi: 10.1164/rccm.200509-1387OC. Epub 2006 Jan 6.


Rationale: Increased oxidative stress is involved in chronic obstructive pulmonary disease (COPD); however, plasma and bronchial lining fluid contains the antioxidant extracellular superoxide dismutase. Approximately 2% of white individuals carry the R213G polymorphism in the gene encoding extracellular superoxide dismutase, which increases plasma extracellular superoxide dismutase 10-fold and presumably also renders bronchial lining fluid high in extracellular superoxide dismutase.

Objective: We tested the hypothesis that R213G reduces the risk of COPD.

Methods: We studied cross-sectionally and prospectively (during 24 yr) 9,258 individuals from the Danish general population genotyped for R213G.

Measurements: We determined plasma extracellular superoxide dismutase concentration, pulmonary function and COPD diagnosed by means of spirometry or through national hospitalization and death registers.

Main results: In the general population, 97.5% were noncarriers, 2.4% were heterozygotes, and 0.02% were homozygotes. Among R213G noncarriers, extracellular superoxide dismutase plasma concentration was 148+/-52 and 142+/-43 ng/ml (mean+/-SD) in individuals with and without COPD (Student's t test, p=0.02). Among heterozygotes, corresponding concentrations were 1,665+/-498 ng/ml and 1,256+/-379 (p<0.001). The adjusted odds ratio for spirometrically diagnosed COPD in heterozygotes versus noncarriers was 0.5 (95% confidence interval: 0.3-0.9). After stratification, the equivalent adjusted odds ratio was 1.5 (0.3-6.6) among nonsmokers and 0.4 (0.2-0.8) among smokers (p value for interaction=0.10). The adjusted hazard ratio for COPD hospitalization or death during follow-up in heterozygotes versus noncarriers was 0.3 (0.1-0.8).

Conclusions: Extracellular superoxide dismutase R213G heterozygosity protects against development of COPD in the Danish general population. This was observed in smokers, but not in nonsmokers.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cross-Sectional Studies
  • DNA / genetics*
  • Denmark / epidemiology
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume
  • Genetic Markers
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Oxidative Stress / genetics*
  • Polymorphism, Genetic*
  • Prospective Studies
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / epidemiology
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Severity of Illness Index
  • Spirometry
  • Superoxide Dismutase / blood
  • Superoxide Dismutase / genetics*
  • Time Factors


  • Genetic Markers
  • DNA
  • SOD3 protein, human
  • Superoxide Dismutase