Genetically increased antioxidative protection and decreased chronic obstructive pulmonary disease.
BACKGROUND
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.


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


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.
Juul
Klaus
K
Department of Clinical Biochemistry, Herlev University Hospital, Herlev, Denmark.
Tybjaerg-Hansen
Anne
A
Marklund
Stefan
S
Lange
Peter
P
Nordestgaard
Børge G
BG
D000368:Aged; D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D012720:Severity of Illness Index; D013147:Spirometry; D013482:Superoxide Dismutase / Q000097:blood / Q000235:genetics*; D013997:Time Factors
D005819:Genetic Markers; D004247:DNA; C441642:SOD3 protein, human; D013482:Superoxide Dismutase