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Oxidative stress is thought to play a major role in the pathogenesis of chronic obstructive pulmonary disease, characterized by impaired lung function. A large number (≥33) of GT repeats (L-allele) in the gene of the powerful antioxidant enzyme heme oxygenase-1 has been associated with susceptibility to accelerated lung function decline. In contrast, β-carotene may help to protect against accelerated decline. To determine whether high serum levels of β-carotene might counterbalance the greater susceptibility of L-allele carriers, the authors analyzed the annual decline in forced expiratory volume in 1 second (FEV1) in a general population sample of 523 French subjects (20–44 years, 50% men) examined in 1992 and 2000 as part of the European Community Respiratory Health Survey. Analysis of covariance, adjusted for sex as well as baseline age, body mass index, smoking, and FEV1, showed that, among subjects with low β-carotene levels, L-allele carriers experienced a steeper mean FEV1 decline than did noncarriers (mean = −58.8, 95% confidence interval: −73.2, −44.5 vs. mean = −34.7, 95% confidence interval: −38.9, −29.8 ml/year) (p = 0.009), whereas among subjects with high β-carotene levels, the FEV1 decline was not different in L-allele carriers and noncarriers (two-sided p = 0.9). The results suggest that high levels of β-carotene might counterbalance the effects on FEV1 decline of a genetically determined deficiency in antioxidant response. [ABSTRACT FROM AUTHOR]