081 Association of lung function décline with the heme oxygenase-1 gène promoter microstallite polymorphism in a gênerai population sample Results from the European Community Respiratory Health Survey (ECRHS) France

Abstract

Introduction Heme oxygenase (HO1) acts against oxidants which are thought to play a major role in the pathogenesis of chro-nic obstructive pulmonary disease (COPD), characterised by impaired lung function. A (GT)n repeat polymorphism in the HO1 gene promoter can modulate the gene transcription in res-ponse to oxidative stress (Am J Hum Genet 2000 ; 66 : 187-95). We hypothesised that this polymorphism could be associated with the level of lung function and decline in subjects exposed to oxidative agression (smokers). Methods We genotyped 749 French subjects (20-44 yrs, 50% men, 40% never-smokers) examined in both 1992 and 2000 as part of the ECRHS. Lung function was assessed by FEV1 (Forced Expiratory Volume in 1 second) and FEV1/FVC (Forced Ventilatory Capacity) ratio. We compared long (L)-allele carriers ((GT)n > 33 repeats for one or two alleles) to non-carriers. Results Cross-sectionaly, in 2000, L-allele carriers showed lower FEV1/FVC than non-carriers. During the 8-yr period, the mean annual FEVl decline and FEV1/FVC decline were-30.9 ± 31.1 ml/yr and -1.8 ± 6.1%/yr, respectively. FEV1/FVC decline was steeper in L-allele carriers than in non-carriers (-2.6 + 5-5 vs -1.5 ±6.4, p = 0.07). There was a strong interaction between allele L and smoking. In 2000, allele L was associated with lower FEV1 and FEV1/FVC in heavy smokers (≥ 20 cig/day) only (p for interaction=0.07 and 0.002 respectively). Baseline heavy smokers carrying allele L showed the steepest FEV1 decline (-62.0 ± 29.5 ml/yr) and the steepest FEV1/FVC decline (-8.8 ± 5.4%/yr) (p for interaction=0.009 and 0.0006). Conclusions These results suggest that long (L) HO1 gene promoter is associated with susceptibility to airways obstruction espe-cially in heavy smokers.