Genetically increased antioxidative protection and decreased chronic obstructive pulmonary disease
Genetically increased antioxidative protection and decreased chronic obstructive pulmonary disease
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DOI：
10.1164/rccm.200509-1387oc
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发表时间：
2006-04-15
影响因子：
24.7
通讯作者：
Nordestgaard, BG
中科院分区：
文献类型：
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作者：
Juul, K;Tybjærg-Hansen, A;Nordestgaard, BG
基本原理：慢性阻塞性肺疾病（COPD）涉及氧化应激增加;然而，血浆和支气管衬里液含有抗氧化剂细胞外超氧化物歧化酶。大约2%的白色个体在编码细胞外超氧化物歧化酶的基因中携带R213 G多态性，其使血浆细胞外超氧化物歧化酶增加10倍，并且推测还使支气管衬里液中细胞外超氧化物歧化酶升高。我们进行了横向和前瞻性的研究（在24年期间）来自丹麦一般人群的9，258个个体进行R213 G基因分型。我们测定了血浆细胞外超氧化物歧化酶浓度，通过肺功能测定法或通过国家住院和死亡登记册诊断的肺功能和COPD。主要结果：在一般人群中，97.5%为非携带者，2.4%为杂合子，0.02%为纯合子。在R213 G非携带者中，COPD患者和非COPD患者的细胞外超氧化物歧化酶血浆浓度分别为148 +/- 52和142 +/- 43 ng/ml（平均值+/- SD）（Student t检验，p = 0.02）。在杂合子中，相应的浓度为1，665，498 ng/ml和1，256：t379（p < 0.001）。杂合子与非携带者经肺功能测定诊断COPD的校正比值比为0.5（95%置信区间：0.3-0.9）。分层后，非吸烟者的等效调整比值比为1.5（0.3-6.6），吸烟者为0.4（0.2-0.8）（相互作用的p值= 0.10）。COPD住院或死亡的调整后的风险比为0.3（0.1-0.8）在后续的杂合子与noncarriers。结论：细胞外超氧化物歧化酶R213 G杂合性保护对发展的COPD在丹麦的一般人群。这在吸烟者中观察到，但在不吸烟者中没有观察到。
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.