Genetically increased antioxidative protection and decreased chronic obstructive pulmonary disease

被引:84
作者
Juul, K
Tybjærg-Hansen, A
Marklund, S
Lange, P
Nordestgaard, BG
机构
[1] Herlev Univ Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark
[2] Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark
[3] Copenhagen Univ Hosp, Copenhagen, Denmark
[4] Bispebjerg Hosp, Copenhagen City Heart Study, Copenhagen, Denmark
[5] Hvidovre Univ Hosp, Dept Resp Med, DK-2650 Hvidovre, Denmark
[6] Univ Umea Hosp, Dept Clin Chem, S-90185 Umea, Sweden
关键词
chronic obstructive pulmonary disease; epidemiology; genetics; smoking;
D O I
10.1164/rccm.200509-1387OC
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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 :t 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.
引用
收藏
页码:858 / 864
页数:7
相关论文
共 44 条
[1]   Substitution of glycine for arginino-213 in extracellular-superoxide dismutase impairs affinity for heparin and endothelial cell surface [J].
Adachi, T ;
Yamada, H ;
Yamada, Y ;
Morihara, N ;
Yamazaki, N ;
Murakami, T ;
Futenma, A ;
Kato, K ;
Hirano, K .
BIOCHEMICAL JOURNAL, 1996, 313 :235-239
[2]  
[Anonymous], 1984, Acta Med Scand Suppl, V682, P1
[3]  
Appleyard M, 1989, SCAND J SOC MED S41, V170, P1
[4]   Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease [J].
Barreiro, E ;
de la Puente, B ;
Minguella, J ;
Corominas, JM ;
Serrano, S ;
Hussain, SNA ;
Gea, L .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2005, 171 (10) :1116-1124
[5]   Oxidant metabolism in chronic obstructive pulmonary disease [J].
Boots, AW ;
Haenen, GRMM ;
Bast, A .
EUROPEAN RESPIRATORY JOURNAL, 2003, 22 :14S-27S
[6]   Extracellular superoxide dismutase attenuates lipopolysaccharide-induced neutrophilic inflammation [J].
Bowler, RP ;
Nicks, M ;
Tran, K ;
Tanner, G ;
Chang, LY ;
Young, SK ;
Worthen, GS .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2004, 31 (04) :432-439
[7]   Oxidative stress in airways - Is there a role for extracellular superoxide dismutase? [J].
Bowler, RP ;
Crapo, JD .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2002, 166 (12) :S38-S43
[8]   Role of extracellular superoxide dismutase in bleomycin-induced pulmonary fibrosis [J].
Bowler, RP ;
Nicks, M ;
Warnick, K ;
Crapo, JD .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2002, 282 (04) :L719-L726
[9]  
CANTIN A, 1985, EUR J RESPIR DIS, V66, P7
[10]   Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease. [J].
Dekhuijzen, PNR ;
Aben, KKH ;
Dekker, I ;
Aarts, LPHJ ;
Wielders, PLML ;
vanHerwaarden, CLA ;
Bast, A .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1996, 154 (03) :813-816