Association of lung function decline with the heme oxygenase-1 gene promoter microsatellite polymorphism in a general population sample.: Results from the European Community Respiratory Health Survey (ECRHS), France
Association of lung function decline with the heme oxygenase-1 gene promoter microsatellite polymorphism in a general population sample.: Results from the European Community Respiratory Health Survey (ECRHS), France
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DOI：
10.1136/jmg.2005.039743
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发表时间：
2006-08-01
影响因子：
4
通讯作者：
Aubier, M.
中科院分区：
文献类型：
--
作者：
Guenegou, A.;Leynaert, B.;Aubier, M.
诱导型血红素加氧酶（HO-1）作用于氧化剂，氧化剂被认为在慢性阻塞性肺疾病（COPD）的发病机制中起主要作用，其特征是肺功能受损。HO-1基因启动子区的A（GT）n重复多态性可调节氧化应激对基因转录的影响。我们假设这种多态性可能与暴露于氧化攻击（吸烟者）的肺功能水平和下降有关。作为ECRHS的一部分，我们在1992年和2000年检查了749名法国受试者（20 - 44岁，50%男性，40%从不吸烟）的基因型。肺功能评价指标为第1秒用力呼气量（FEV 1）和FEV 1/用力肺活量（FVC）比值。我们比较了长（L）等位基因携带者（对于一个或两个等位基因，（GT）（n）> 33个重复）与非携带者。在横断面上，2000年，L等位基因携带者的FEV 1/FVC低于非携带者。在8年期间，平均年FEV 1和FEV 1/FVC下降分别为-30.9（31.1）ml/年和-1.8（6.1）U/年。L等位基因携带者的FEV 1/FVC下降幅度大于非携带者（-2.6（5.5）vs-1.5（6.4），p = 0.07）。L等位基因与吸烟之间有很强的交互作用。2000年，L等位基因仅与重度吸烟者（>= 20支烟/天）的FEV 1和FEV 1/FVC较低相关（相互作用p分别= 0.07和0.002）。携带L等位基因的基线重度吸烟者表现出最快的FEV 1下降（-62.0（29.5 ml/年））和最快的FEV 1/FVC下降（-8.8（5.4 U/年）（相互作用p = 0.009和0.0006）。这些结果表明，在重度吸烟者中长（L）HO-1基因启动子与气道阻塞的易感性相关。
Inducible heme oxygenase (HO-1) acts against oxidants that are thought to play a major role in the pathogenesis of chronic obstructive pulmonary disease ( COPD), characterised by impaired lung function. A (GT) n repeat polymorphism in the HO-1 gene promoter can modulate the gene transcription in response to oxidative stress. We hypothesised that this polymorphism could be associated with the level of lung function and decline in subjects exposed to oxidative agression ( smokers). We genotyped 749 French subjects ( 20 - 44 years, 50% men, 40% never smokers) examined in both 1992 and 2000 as part of the ECRHS. Lung function was assessed by forced expiratory volume in 1 second (FEV1) and FEV1/forced ventilatory capacity (FVC) ratio. We compared long (L) allele carriers ((GT)(n) > 33 repeats for one or two alleles) to non-carriers. Cross sectionally, in 2000, L allele carriers showed lower FEV1/FVC than non-carriers. During the 8 year period, the mean annual FEV1 and FEV1/FVC declines were -30.9 (31.1) ml/year and -1.8 (6.1) U/year, respectively. FEV1/FVC decline was steeper in L allele carriers than in non-carriers (-2.6 (5.5) v -1.5 (6.4), p = 0.07). There was a strong interaction between the L allele and smoking. In 2000, the L allele was associated with lower FEV1 and FEV1/FVC in heavy smokers (>= 20 cigarettes/day) only (p for interaction = 0.07 and 0.002 respectively). Baseline heavy smokers carrying the L allele showed the steepest FEV1 decline (-62.0 (29.5 ml/year) and the steepest FEV1/FVC decline (-8.8 (5.4 U/ year) ( p for interaction = 0.009 and 0.0006). These results suggest that a long ( L) HO-1 gene promoter in heavy smokers is associated with susceptibility to develop airway obstruction.