Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers
Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers
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DOI：
10.1165/rcmb.2002-0321oc
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发表时间：
2003-09-01
影响因子：
6.4
通讯作者：
Crystal, RG
中科院分区：
文献类型：
--
作者：
Hackett, NR;Heguy, A;Crystal, RG
吸烟是发展慢性支气管炎的主要危险因素，但只有15-20%的吸烟者发展这种疾病。由于氧化剂是吸烟引起的气道损伤的主要机制，我们假设吸烟与气道上皮细胞中各种抗氧化剂相关基因的上调有关，但反应的幅度显示出很高的个体间差异。微阵列分析用于评估支气管镜检查获得的匹配队列（13名当前吸烟者，9名非吸烟者）的气道上皮中4类（过氧化氢酶/超氧化物歧化酶家族;谷胱甘肽代谢;氧化还原平衡;和磷酸戊糖循环）中44种抗氧化剂相关基因的表达水平，其中无一人患有肺部疾病。在同一个体内（右肺与左肺或随着时间的推移），基因表达水平变化极小，但与非吸烟者相比，吸烟者上皮中16/44抗氧化剂相关基因显著上调。吸烟者的亚组被确定为具有抗氧化剂相关基因表达水平的簇。我们建议，抗氧化剂相关的基因表现出最大的变化，在吸烟者的表达水平可能是有用的遗传标记，在流行病学研究评估吸烟引起的慢性支气管炎的易感性。
Cigarette smoking is the major risk factor for developing chronic bronchitis, yet only 15-20% of smokers develop this disorder. Because oxidants are the major mechanism of smoking-induced airway damage, we hypothesized that smoking is associated with upregulation of various antioxidant-related genes in the airway epithelium, but the magnitude of the response shows high interindividual variability. Microarray analysis was used to assess levels of expression of 44 antioxidant-related genes in four categories (catalase/superoxide dismutase family; glutathione metabolism; redox balance; and pentose phosphate cycle) in bronchoscopy-obtained airway epithelium of matched cohorts (13 current smokers, 9 nonsmokers), none of whom had lung disease. There was minimal variation in gene expression levels within the same individual (right versus left lung or over time), but significant upregulation of 16/44 antioxidant-related genes in smoker epithelium compared with nonsmokers. Subgroups of smokers were identified with clusters of expression levels of antioxidant-related genes. We propose that the antioxidant-related genes demonstrating the most variability in the level of expression in smokers may be useful genetic markers in epidemiologic studies assessing susceptibility to smoking-induced chronic bronchitis.