Abstract

Paraoxonase-1 (PON1) is a high-density, lipoprotein-associated, multifunctional antioxidant enzyme that is detected in nonciliated bronchiolar epithelial cells, although its role in the lung has not yet been clarified. We therefore investigated the association between the PON1 Q192R polymorphism and lung function. A total of 216 male Saskatchewan grain handlers provided demographic, occupational and respiratory-symptom information by means of questionnaires, and thereafter underwent PON1 Q192R genotyping and lung-function testing. Mean lung-function values did not differ among the Q192R genotypes. However, current smokers with the Q/Q genotype had a higher mean percent predicted forced expiratory volume in the first second (FEV(1)), and absolute and percent predicted FEV(1) per forced vital capacity (FVC) compared with current smokers with at least one 192R allele (100.9 +/- 11.2% vs 92.0 +/- 15.1%, p = 0.01; 78.0 +/- 5.9% vs 74.1 +/- 6.8%, p = 0.03; and 96.8 +/- 7.1% vs 92.1 +/- 8.3%, p = 0.03; respectively). The incidence of subjects with FEV(1)/FVC less than 70% was significantly higher in current smokers with at least one 192R allele than in nonsmokers with the Q/Q genotype (odds ratio: 5.0; 95% confidence interval: 1.5-17.4). The protective effect of the Q/Q genotype was not found in nonsmokers. The FVC was not influenced by either PON1 genotype or smoking status. The results obtained from grain handlers suggest that PON1 may play some role in the protection of the airways against the toxicity of cigarette smoke, and the 192R allele may be a novel genetic risk factor for airway injury.

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