[Association of lung function decline with the microsatellite polymorphism in the heme oxygenase-1 gene promoter, in a general population sample. Results from the Longitudinal European Community Respiratory Health Survey (ECRHS-France)].
Heme oxygenase (HO1) acts against oxidants which are thought to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD). A (GT)n repeat polymorphism in the HO1 gene promoter can modulate the transcription of this gene in response to oxidative stress. We postulated that this polymorphism might be associated with the degree and decline of lung function in subjects exposed to oxidative stress (smokers). We genotyped 749 French subjects (20-44 years, 50% men, 40% never-smokers) who were examined in both 1992 and 2000 as part of the ECRHS. Lung function was assessed by measuring FEV1 (Forced Expiratory Volume in 1 second) and the FEV1/FVC (Forced Ventilatory Capacity) ratio. We compared long (L)-allele carriers ((GT)n > or = 33 repeats for one or two alleles) to non-carriers. During the 8-year study period, the mean annual FEV1 and FEV1/FVC declines were -30.9 +/- 31.1 ml/year and -1.8 +/- 6.1 units/year, respectively. The 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 values in heavy smokers (J20 cig/day) only (p for the interactions, 0.07 and 0.002 respectively). Baseline heavy smokers carrying allele L showed the steepest FEV1 decline (-62.0 +/- 29.5 ml/year) and the steepest FEV1/FVC decline (-8.8 +/- 5.4 units/year) (p for the interactions, 0.009 and 0.0006). These results suggest that a long (L) HO1 gene promoter increases the risk of airway obstruction in heavy smokers.
Aubier
Michel
M
INSERM U700, Faculté de Médecine Xavier Bichat, 16 rue Henri Huchard, 75018 Paris.
Guenegou
Armelle
A
Benessiano
Joëlle
J
Leynaert
Bénédicte
B
Boczkowski
Jorge
J
Neukirch
Françoise
F
D000328:Adult; D000483:Alleles; D005260:Female; D005541:Forced Expiratory Volume; D005602:France; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D018895:Microsatellite Repeats; D015337:Multicenter Studies as Topic; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000235:genetics; D012129:Respiratory Function Tests; D012131:Respiratory Insufficiency / Q000209:etiology* / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
D051547:Heme Oxygenase-1