Genotypes in matrix metalloproteinase 9 are a risk factor for COPD.
A growing body of evidence indicates that matrix metalloproteinases (MMPs) play a role in the pathogenesis of COPD. Therefore, we conducted a candidate gene association study of 4 promoter polymorphisms that are known to modify expression levels of the MMP-1, MMP-2, and MMP-9 genes and a Gln279Arg polymorphism in exon 6 of MMP-9 that modifies the substrate-binding region. We examined the association of each variant and haplotypes in 385 male veterans with greater than 20 pack-years of cigarette smoking whose COPD status was characterized using spirometry. The association of these polymorphisms was also examined with decline of pulmonary function in a subset of participants. Only the 279Arg variant was more common in participants with COPD and the homozygous variant was associated with a 3-fold increased risk for COPD. In the haplotype analysis, the haplotype comprising the 249Arg and the CA promoter polymorphism within the MMP-9 gene was associated with risk, suggesting that either 279Arg or a linked variant on this haplotype underlies the association. No association of this polymorphism was found with decline in pulmonary function. These studies show that variants of the MMP-9 gene are associated with COPD in this cohort of veterans.
Tesfaigzi
Yohannes
Y
Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive, SE, Albuquerque, NM 87108, USA. ytesfaig@lrri.org
Myers
Orrin B
OB
Stidley
Christine A
CA
Schwalm
Kurt
K
Picchi
Maria
M
Crowell
Richard E
RE
Gilliland
Frank D
FD
Belinsky
Steven A
SA
D000328:Adult; D000368:Aged; D001483:Base Sequence / Q000235:genetics; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D017720:Molecular Epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D015206:Southwestern United States / Q000453:epidemiology
D020780:Matrix Metalloproteinase 9