Kobylecki Camilla J, Afzal Shoaib, Nordestgaard Børge G
1 Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital , Herlev, Denmark .
2 Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital , Copenhagen, Denmark .
Antioxid Redox Signal. 2016 May 20;24(15):884-91. doi: 10.1089/ars.2016.6629. Epub 2016 Feb 22.
The extracellular superoxide dismutase (SOD3, EC-SOD) enzyme is a major extracellular scavenger of the superoxide anion, a free radical with the potential to cause oxidative damage. Previously, R213G heterozygosity has been associated with a decreased risk of chronic obstructive pulmonary disease (COPD) and an increased risk of ischemic heart disease (IHD). We questioned whether SOD3 R213G homozygosity (213GG) influences morbidity, mortality, and lung function. We found 14 R213G homozygotes (213GG) among 95,871 individuals (1/7000) from the Copenhagen General Population Study and the Copenhagen City Heart Study. The hazard ratio for homozygotes versus noncarriers (NC) (213RR) was 2.8 (95% confidence interval: 1.2-6.8, p = 0.02) for IHD, 1.8 (0.7-4.8, p = 0.25) for any form of cancer, and 2.3 (0.9-6.2, p = 0.10) for all-cause mortality. R213G heterozygosity was not associated with morbidity or mortality. Among never-smokers, we found a 20% lower forced expiratory volume in 1 s (FEV1)% predicted (p = 0.003), a 16% lower FVC% predicted (p = 0.01), and a 7% lower FEV1/FVC ratio (p = 0.02) in R213G homozygotes compared to NC. Our results lead to the hypotheses that the SOD3 enzyme plays a role in cardiovascular disease and in impairing and maintaining lung function in never-smokers. However, our findings should be retested in larger studies and in nonsmoking COPD patient cohorts. Antioxid. Redox Signal. 24, 884-891.
细胞外超氧化物歧化酶（SOD3，胞外超氧化物歧化酶）是超氧阴离子的主要细胞外清除剂，超氧阴离子是一种可能导致氧化损伤的自由基。此前，R213G杂合性与慢性阻塞性肺疾病（COPD）风险降低以及缺血性心脏病（IHD）风险增加有关。我们质疑SOD3 R213G纯合性（213GG）是否会影响发病率、死亡率和肺功能。我们在哥本哈根普通人群研究和哥本哈根市心脏研究的95,871名个体（1/7000）中发现了14名R213G纯合子（213GG）。纯合子与非携带者（NC）（213RR）相比，IHD的风险比为2.8（95%置信区间：1.2 - 6.8，p = 0.02），任何形式癌症的风险比为1.8（0.7 - 4.8，p = 0.25），全因死亡率的风险比为2.3（0.9 - 6.2，p = 0.10）。R213G杂合性与发病率或死亡率无关。在从不吸烟者中，我们发现R213G纯合子的第1秒用力呼气量（FEV1）预测值降低了20%（p = 0.003），用力肺活量（FVC）预测值降低了16%（p = 0.01），FEV1/FVC比值降低了7%（p = 0.02），与NC相比。我们的结果得出以下假设：SOD3酶在心血管疾病以及从不吸烟者的肺功能损害和维持中起作用。然而，我们的发现应在更大规模的研究和非吸烟COPD患者队列中重新进行验证。《抗氧化与氧化还原信号》24，884 - 891。
