Matrix metalloproteinase-9 promoter polymorphism associated with upper lung dominant emphysema.
BACKGROUND
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.


OBJECTIVE
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.


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.
Ito
Isao
I
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Shogoin-kawaharacho 54, Sakyo-ku, Kyoto, 606-8507, Japan. nagai@kuhp.kyoto-u.ac.jp
Nagai
Sonoko
S
Handa
Tomohiro
T
Muro
Shigeo
S
Hirai
Toyohiro
T
Tsukino
Mitsuhiro
M
Mishima
Michiaki
M
D000368:Aged; D000483:Alleles; D004247:DNA / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics*; D012307:Risk Factors; D014057:Tomography, X-Ray Computed
D004247:DNA; D020780:Matrix Metalloproteinase 9