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Published ahead of print on August 26, 2005, doi:10.1164/rccm.200506-953OC
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American Journal of Respiratory and Critical Care Medicine Vol 172. pp. 1378-1382, (2005)
© 2005 American Thoracic Society
doi: 10.1164/rccm.200506-953OC

Original Article

Matrix Metalloproteinase-9 Promoter Polymorphism Associated with Upper Lung Dominant Emphysema

Isao Ito, Sonoko Nagai, Tomohiro Handa, Shigeo Muro, Toyohiro Hirai, Mitsuhiro Tsukino and Michiaki Mishima

Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Correspondence and requests for reprints should be addressed to Sonoko Nagai, M.D., Ph.D., Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Shogoin-kawaharacho 54, Sakyo-ku, Kyoto, 606-8507, Japan. E-mail: nagai{at}kuhp.kyoto-u.ac.jp

Rationale: Matrix metalloproteinase 9 (MMP-9) has proteolytic activity against connective tissue proteins and appears to play an important role in the development of chronic obstructive pulmonary disease (COPD). The functional polymorphism of MMP-9 (C-1562T) is considered as one of the candidate genes in the susceptibility to COPD.

Objectives: To determine if MMP-9 (C-1562T) is related to the development of COPD in the Japanese population and whether it is associated with development of pulmonary emphysema assessed by high-resolution computed tomographic (HRCT) parameters.

Methods: MMP-9 (C-1562T) genotypes of 84 patients with COPD and 85 healthy smokers (control subjects) were determined by the restriction fragment length polymorphism method. We investigated the relationship between the genotypes using automatically analyzed HRCT parameters, such as percentage of low attenuation area (LAA%) and average computed tomography (CT) value density (Hounsfield units; mean CTv) in upper, middle, and lower lung fields in all patients with COPD.

Measurements and Main Results: There was no difference in polymorphism of MMP-9 (C-1562T) between patients with COPD and control subjects. In the HRCT study, patients with COPD with a T allele (C/T or T/T) showed larger LAA% (95% confidence interval of difference, 0.5–18.7; p = 0.04), and smaller mean CTv (confidence interval, –34.3 to –1.0; p = 0.04) in the upper lung compared with patients without T alleles (C/C). However, pulmonary function tests showed no difference between the two patient groups. Patients with a T allele showed a decrease in LAA% and an increase in mean CTv from upper to lower lung fields (p = 0.006 and p = 0.002, respectively).

Conclusions: Polymorphism of MMP-9 (C-1562T) was associated with upper lung dominant emphysema in patients with COPD.

Key Words: chronic obstructive pulmonary disease • high-resolution computed tomography • low attenuation area % • mean CT value




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