Genetic polymorphism in matrix metalloproteinase-9 and pulmonary emphysema

Protease-antiprotease imbalance due to genetic variation may be responsible for the development of pulmonary emphysema induced by smoking. Since matri x metalloproteinases (MMPs) have recently been suggested to play important roles in the pathogenesis of pulmonary emphysema, the association between t he functional polymorphism of MMP-9 (-1562C/T) and the development of pulmo nary emphysema was examined in 110 smokers and 94 nonsmokers in Japan. The T allele frequency was higher in subjects with distinct emphysema on chest CT-scans (n = 45) than in those without it (n = 65) (0.244 vs 0.123, P = 0. 02). Logistic regression analysis demonstrated that the T allele is a risk factor for smoking-induced emphysema (odds ratio = 2.69, P = 0.02). DLCO/VA was lower (P = 0.02) and emphysematous changes were more conspicuous (P = 0.03) in subjects with C/T or T/T (n = 35) than in those with C/C (n = 75). These results suggest that the polymorphism of MMP-9 acts as a genetic fac tor for the development of smoking-induced pulmonary emphysema. (C) 2001 Ac ademic Press.